Accommodating lens with cavity

ABSTRACT

A lens comprises an internal cavity structure formed by dissolution of a soluble insert material. The internal soluble material may dissolve through a body of a lens such as a contact lens in order to form the cavity within the contact lens. The cavity within the lens can be shaped in many ways, and corresponds to the shape of the dissolved material, such that many internal cavity shapes can be readily fabricated within the contact lens. The insert can be placed in a mold with a pre-polymer material, and the pre-polymer material cured with the insert placed in the mold to form the lens body. The polymerized polymer may comprise a low expansion polymer in order to inhibit expansion of the lens when hydrated. The polymer may comprise a hydrogel when hydrated. The soft contact lens material comprises a sufficient amount of cross-linking to provide structure to the lens and shape the cavity.

CROSS-REFERENCE

This application is a continuation application of PCT/US2016/061700,filed on 11 Nov. 2016, entitled “ACCOMMODATING LENS WITH CAVITY”, whichis a non-provisional of, and claims the benefit of U.S. Prov. Ser. App.No. 62/327,938, filed on 26 Apr. 2016, entitled “ACCOMMODATING LENS WITHCAVITY”, and U.S. Prov. Ser. App. No. 62/254,093, filed on 11 Nov. 2015,entitled “ACCOMMODATING LENS WITH CAVITY”, the entire disclosures ofwhich are incorporated herein by reference.

The subject matter of the present application is related to thefollowing patent applications: PCT/US2014/013427, filed on 28 Jan. 2014,entitled “Accommodating Soft Contact Lens”; PCT/US2014/013859, filed onJan. 30, 2014, entitled “Manufacturing Process of an AccommodatingContact Lens”; PCT/US2014/071988, filed on Dec. 22, 2014, entitled“Fluidic Module For Accommodating Soft Contact Lens”; U.S. applicationSer. No. 62/031,324, filed Jul. 31, 2014, entitled “Sacrificial MoldingProcess for an Accommodating Contact Lens”; PCT/US2015/0433307, filed 31Jul. 2015, entitled “LOWER LID ACTIVATING AN ELECTRONIC LENS”;PCT/US2016/061696, filed on Nov. 11, 2016, entitled “SOFT CONTACT LENSMATERIAL WITH LOW VOLUMETRIC EXPANSION UPON HYDRATION”; andPCT/US2016/061697, filed on Nov. 11, 2016, entitled “ROTATIONALLYSTABILIZED CONTACT LENS”; the entire disclosures of which areincorporated herein by reference.

The subject matter of the present application is also related to thefollowing provisional patent applications: U.S. Prov. Ser. App. No.62/254,048, filed on 11 Nov. 2015, entitled “SOFT CONTACT LENS MATERIALWITH LOW VOLUMETRIC EXPANSION UPON HYDRATION”; U.S. Prov. Ser. App. No.62/254,080, filed on 11 Nov. 2015, entitled “ROTATIONALLY STABILIZEDCONTACT LENS”; and U.S. Prov. Ser. App. No. 62/255,242, filed on 13 Nov.2015, entitled “ROTATIONALLY STABILIZED CONTACT LENS”, the entiredisclosures of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

The prior methods and apparatus for forming manufacturing lenses such ascontact lenses can be less than ideal in at least some respects. Forexample, contact lenses with internal fluidic structures such aschambers can be challenging to manufacture in at least some instances.Although structures such as balloons or modules can be embedded withincontact lenses, such structures can make the manufacturing processsomewhat more involved than would be ideal.

Multifocal contact lenses may be of two types of designs: those whichprovide simultaneous vision (U.S. Pat. No. 7,517,084, U.S. Pat. No.7,322,695, both by Wooley, et al) and those that provide alternatingvision (U.S. Pat. No. 7,503,652, U.S. Pat. No. 6,092,899, U.S. Pat. No.7,810,925, by Evans, et al). Both types of contact lenses may have atleast two or more optical zones of different focal lengths. Simultaneousvision can be provided by multifocal contact lenses that have opticalzones of different focusing power disposed radially symmetrically aboutthe optical center of the lens which is also frequently its geometricalcenter. Alternating vision can be provided by designs in which theoptical zones are separated from each other, typically along thevertical meridian, so that the optical center of each zone comes inalignment with the pupillary center as the lens is translated upwardsduring downward gaze. Neither approach is well accepted by wearers ofcontact lenses, and there is a continuing unmet need for anaccommodating contact lens with a dynamically variable optic that has asingle variable focal length, which is easily worn and used. The imagequality provided by an accommodating contact lens that can be easilyadjusted by the wearer should be much better than multifocal lenses.

A prior contact lens design has been described by Iuliano (U.S. Pat. No.7,699,464 B2). The manufacture of such a device can be more complicatedthan would be ideal. Earlier, Elie disclosed an accommodating contactlens (WO 1991010154 A1).

Accommodating contact lenses have been proposed in which a centralchamber increases curvature when an eyelid engages a lower chambercoupled to the central chamber. The prior lenses may have less thanideal optical performance, and can be more difficult to use andmanufacture than would be ideal. In some instances, the prior contactlenses may provide less than ideal responses to eyelid pressure, and maynot change shape in response to eyelid pressure as readily as would beideal. Also, portions of the lens can be formed in stages and differentpieces brought together to form the lens, which results in additionalsteps in the manufacturing process. Although modules embedded inaccommodating contact lenses can be effective, such modules can resultin greater complexity and cost than would be ideal. Also, embeddedmodules may provide non-ideal amounts of resistance to movement of thestructures of an accommodating contact lens, depending upon thestiffness of the tensile modulus of the membrane comprising the module.

In light of the above, improved contact lenses and methods ofmanufacture are needed. Ideally, such contact lenses and methods ofmanufacture would provide contact lenses that change shape withdecreased amounts of pressure, involve fewer steps and allow contactlenses to be produced in large quantities with internal cavitystructures.

SUMMARY OF THE INVENTION

Although reference is made to accommodating contact lenses, the lenses,methods, and apparatus disclosed herein can be used with many lenses,such as intraocular lenses, and accommodating intraocular lenses. Thematerial having a cavity as described herein will have many applicationsin many fields, such as implants for sensors and drug delivery. Thecavity can be formed in a body comprising polymer material that allowsthe contents of the cavity to be in equilibrium with an externalsolution prior to use, and can allow an exchange of fluid between thecavity and external liquid when placed on a subject.

The lens comprises an internal cavity structure formed by dissolution ofa soluble insert material. The internal soluble material may dissolvethrough a body of a lens such as a contact lens in order to form thecavity within the contact lens. The cavity within the lens can be shapedin many ways, and corresponds to the shape of the dissolved material,such that many internal cavity shapes can be readily fabricated withinthe contact lens. The insert can be placed in a mold with a pre-polymermaterial, and the pre-polymer material cured with the insert placed inthe mold to form the lens body. The polymerized polymer may comprise alow expansion polymer in order to inhibit expansion of the lens whenhydrated. The polymerized material can be hydrated and the insertdissolved in order to form the cavity with the desired shape within thelens body. The polymer may comprise a hydrogel when hydrated. The softcontact lens material comprises a sufficient amount of cross-linking toprovide structure to the lens and shape the cavity, and allows water andsolutes to diffuse in and out of the cavity in order to establishequilibrium of the cavity with the external environment of the lensbody. The insert comprise a molecular weight sufficiently low to diffuseout of the lens body when hydrated, and sufficiently high to providestrength to the insert for handling and placement in the lens mold. Thediffusion of the dissolved insert material away from the cavity mayinhibit osmotic pressure and expansion of the cavity as the materialdissolves, such that the structural integrity of the contact lens andcavity can be preserved. After dissolution of the insert, the shape ofthe cavity corresponds to the three dimensional shape profile of theinsert material, such that the cavity can be shaped in many ways.

The internal cavity may comprise an inner optical chamber and a lowerchamber of an accommodating contact lens, with a channel extending therebetween. When the lower eyelid engages the lower chamber, fluid ispassed to the optical chamber so as to increase the curvature of theoptical chamber and provide optical power for near vision.

The chamber of the contact lens can be configured in many ways. Thechamber may provide hydration to the eye with release of water throughthe lens body to the eye in order to hydrate the eye. The chamber maycomprise a drug to treat the eye, and the drug can be released from thechamber through the lens body to treat the eye. The cavity can be formedover at least a portion of a sensor embedded within the contact lens inorder to improve coupling of the sensor to the external environment ofthe lens.

The contact lens can be provided with a sterile package in which asterile fluid contained in the sterile package and the contact lensimmersed in the fluid. The cavity of the contact lens can be inequilibrium with the fluid in which the contact lens is immersed.

In a first aspect, a soft contact lens for correcting vision of an eyeis provided. The soft contact lens comprises a hydrogel contact lensbody comprising water and cross-linked polymer. The contact lens bodydefines an internal cavity comprising a fluid. The cross-linked polymerallows water to diffuse in and out of the contact lens body to thecavity from an external surface of the body. The cavity is shaped tocorrect vision when in equilibrium with tear fluid of the eye.

In many embodiments, the hydrogel contact lens body and cavity may beconfigured together to increase optical power by at least 2 D with anincrease in internal pressure within a range from about 20 Pascals (Pa)to about 50 Pa. The cavity may comprise a volume containing the fluidwithin a range from about 0.5 mm³ to about 5 mm³. The hydrogel contactlens body may comprise a modulus within a range from about 0.25 MPa toabout 2 MPa. A hydrogel material of the contact lens body may comprisean equilibrium water content within a range from about 30% to about 70%.

In many embodiments, hydrogel contact lens body may comprise internalsurfaces defining the cavity. The internal surfaces may compriseinternal surface structures defined with erosion of a material fromwithin the cavity.

In many embodiments, the hydrogel contact lens body may comprise a firstportion on a first side of the cavity and a second portion of the secondside of the cavity with the cavity extending therebetween, the firstportion bonded to the second portion away from the cavity to containfluid within the cavity. An interface of the first material bonded tothe second material may optionally be detectable by dark fieldmicroscopy.

In many embodiments, the cross-linked polymer may directly contactsliquid of the cavity.

In many embodiments, the polymer may comprise sufficient stiffness toretain a shape of an insert dissolved from within the lens body to formthe cavity.

In many embodiments, the cavity may comprise a dissolved material havinga molecular weight within a range from about 3 to 7 k Daltons. Thedissolved material may be capable of diffusing through said polymer ofsaid contact lens body. Said dissolved material may further comprise amaterial of an insert dissolved to form the cavity. Said cavity maycomprise a shape profile corresponding to the dissolved insert.

In many embodiments, the cavity may comprise an optical portionconfigured to correct vision of the eye and a lower portion fluidicallycoupled to the optical portion. The optical portion may be configured toprovide near vision correction when an eyelid engages the lower portion.The polymer may comprise a sufficient amount of cross-linking to retainfluid in the optical portion when the lower portion engages the eyelidto correct near vision of the eye. Alternatively or in combination saidcontact lens body may comprise one or more hinges coupled to saidoptical portion and said lower portion.

In many embodiments, the cavity may comprise one or more internalstructures shaped with an erodible material.

In many embodiments, the polymer may comprise hydrogel.

In many embodiments, the cavity may be filled with a liquid and nothermetically sealed. The contact lens body may be permeable to a fluidin which the lens is packaged and the cavity may be in equilibrium withthe fluid.

In many embodiments, the polymer may comprise a homogeneous polymer.

In many embodiments, the polymer may comprise a homopolymer.

In many embodiments, the polymer may comprise hydrogel.

In many embodiments, the polymer may comprise channels sized to permitdiffusion of water between the cavity and outside the lens body and toinhibit bacteria from entering the cavity from outside the lens body.

In many embodiments, the polymer may allow molecules having a radius ofgyration of no more than 50 nm to diffuse through said polymer of thelens body. The polymer may allow molecules having a radius of gyrationof no more than 15 nm to diffuse through the polymer of said lens body.

In many embodiments, the cavity may comprise a dissolved material havinga molecular weight within a range from about 3 to 10 k Daltons. Thedissolved material may be capable of diffusing through said polymer ofsaid contact lens body.

In many embodiments, the cavity may comprise a volume within a rangefrom about 1 to 5 uL.

In many embodiments, the contact fluid may comprise a refractive indexwithin a range from about 1.31 to about 1.37 and the contact lens bodymay comprise an index of refraction within a range from about 1.37 toabout 1.48.

In many embodiments, the hydrogel contact lens may have an anterior sidewith an anterior thickness defined between an anterior surface of thecontact lens body and an anterior surface of the internal cavity. Thehydrogel contact lens may have a posterior side with a posteriorthickness defined between a posterior surface of the contact lens bodyand a posterior surface of the inner cavity. The anterior thickness maybe less than the posterior thickness. The anterior thickness may bewithin a range defined between any two of the following values: about 10microns, about 25 microns, about 50 microns, about 100 microns, about150 microns, and 200 microns. The posterior thickness may be within arange defined between any two of the following values: about 10 microns,about 100 microns, and about 200 microns. A thickness of the internalcavity from the anterior surface to the posterior surface thereof may bewithin a range defined between any two of the following values: about0.5 microns, about 15 microns, about 50 microns, and about 100 microns.A thickness of the contact lens body from the anterior surface to theposterior surface thereof may be in a range from about 80 microns toabout 250 microns.

In many embodiments, a shape changing portion of the lens used tocorrect vision may have RMS optical path difference aberrations of about0.4 microns or less in a far vision configuration when placed on an eye.

In many embodiments, an inner surface of the polymer defining the cavitycomprises a shape profile corresponding to a solid material dissolved toform said cavity. The inner surface of said polymer defining said cavitymay further comprise structure corresponding to the solid materialdissolved to form said cavity. Alternatively or in combination, theinner surface of the cavity comprises an optically smooth surface overan inner portion of the cavity through which light passes to correctvision. The optically smooth surface may have a wavefront distortion ofabout 0.3 microns or less measured through the optically smooth surface.The optically smooth surface may comprise no visually perceptibleartifacts when worn by a patient. The optically smooth surface may havean RMS value of about 0.2 microns or less. The inner surface of thecavity may comprise a residual surface structure from the solid materialdissolved to form said cavity. The inner surface of the cavity may havean RMS value of about 50 nm or less. The inner surface of the cavity mayhave an RMS value in a range defined between any two of the followingvalues: about 5 nm, about 10 nm, about 15 nm, about 300 nm, about 500nm, and about 1000 nm.

In another aspect, a soft contact lens package is provided. The softcontact lens package comprises a sterile package, an aqueous fluidcontained within the package, and a soft contact lens. The soft contactlens comprises a contact lens body. The contact lens body comprises ahydrogel material contained within the package. The contact lens body isimmersed in the fluid contained within the package. The contact lensbody defines a cavity within said body, said cavity comprising a liquid.The contact lens body is permeable to the liquid and the fluid in whichthe contact lens is immersed such that the cavity is in equilibrium withthe fluid outside the lens body.

In many embodiments, at least a portion of the fluid may have diffusedinto said cavity.

In many embodiments, the contact lens body may be permeable to watersuch that said contact lens hydrates an eye with fluid from the cavitywhen placed on the eye.

In many embodiments, the contact lens body may comprise an index ofrefraction within a range from about 1.31 to about 1.37. The contactlens body may comprise an index of refraction within a range from about1.37 to about 1.48. The fluid may comprise an index of refraction withina range from about 1.31 to about 1.37.

In many embodiments, the contact lens body may comprise an amount ofcross-linking sufficient to inhibit bacteria entering the cavity fromoutside the contact lens body.

In another aspect, an accommodating soft contact lens is provided. Thelens comprises an embedded cavity filled with the fluid of hydration ofsaid lens.

In many embodiments, the lens may generate an addition plus power on eyeupon down-gaze when viewing near objects. The range of said add powermay be 0.5 D to 6.0 D. Alternatively or in combination, said down-gazemay be in the range of 10 degrees to 40 degrees. Alternatively or incombination, said object distance may be in the range 15 cm to 200 cm.

In many embodiments, the lens may comprise a cross-linked hydrogelnetwork formed from a photo-polymerizable pre-polymer formulation. Thehydrogel may have an amount of water within a range from about 28% to65%.

In many embodiments, the cavity may comprise a drug.

In many embodiments, the cavity may comprise timolol.

In many embodiments, the lens may further comprise a sensor. At least aportion of the sensor may be located within the cavity.

In many embodiments, the lens may further comprise a sensor. At least aportion of the sensor may be located within the cavity. The sensor maycomprise one or more of a pressure sensor, a glucose sensor, a biomarkersensor, an electrical sensor, or a sensor having ion specificmicroelectrodes. The sensor may comprise a volume of no more than about0.001 mm³.

In another aspect, a method of manufacturing a lens is provided. Themethod comprises dissolving an insert from within a polymerized lensmaterial to form a cavity within the polymerized lens material. In manyembodiments, the method further comprises polymerizing a pre-polymermaterial to form the polymerized material and hydrating the polymerizedlens material with the insert contained therein.

In many embodiments, the pre-polymer material may be polymerized withlight.

In many embodiments, the method further may comprise placing the insertand the pre-polymer material to cure the pre-polymer with the insertplaced in the mold.

In many embodiments, the insert may comprise a biocompatible watersoluble polymer. The biocompatible water soluble polymer may compriseone or more of polyvinyl alcohol, polyvinyl acetate, polyethylene oxide,propylene oxide, copolymer of ethylene and propylene oxides (Pluronicacids), poly vinyl pyrollidone, polyethylene imine, polyacrylamide, orpolysaccharide.

In many embodiments, the insert may comprise a biocompatible watersoluble polymer. The biocompatible water soluble polymer may compriseone or more of polyvinyl alcohol, polyvinyl acetate, polyethylene oxide,propylene oxide, copolymer of ethylene and propylene oxides (Pluronicacids), poly vinyl pyrollidone, polyethylene imine, polyacrylamide,polysaccharide, polyethylene glycol (PEG) in the molecular weight rangeof about 600 g/mol to about 6000 g/mol, hydrophilic ionic polyacrylates,polymethacrylates, or copolymers of hydrophilic ionic polyacrylates andpolymethacrylates.

In many embodiments, the pre-polymer may comprise one or more of amonomer or an oligomer.

In many embodiments, the polymerized lens material may comprise ahomopolymer.

In many embodiments, the polymerized lens material may comprise a lowexpansion polymer.

In many embodiments, the insert may comprise a substantially uniformthickness.

In many embodiments, the insert may comprise a substantially uniformthickness and curved upper and lower surfaces having a curvaturecorresponding to a curvature of a mold defining a base curvature of thecontact lens.

In many embodiments, the insert may comprise a thickness and a shapeprofile corresponding to the cavity.

In many embodiments, the insert may comprise a material having amolecular weight within a range from about 3 k Daltons to about 10 kDaltons and wherein said material dissolves and diffuses through saidpolymerized lens material to form the cavity within said polymerizedlens material.

In many embodiments, the insert may comprise a material having amolecular weight of at least about 3 k Daltons to add stiffness to thematerial to retain a shape. The cavity may correspond to the shape ofthe insert.

In many embodiments, the lens may comprise a cross-linked hydrogelnetwork formed from a photo-polymerizable pre-polymer formulation. Thehydrogel may comprise an amount of hydration within a range from about28% to about 65%.

In another aspect, a soft contact lens for correcting vision of an eyeis provided. The soft contact lens comprises a hydrogel contact lensbody comprising water and cross-linked polymer. The contact lens bodydefines an internal cavity comprising a fluid. The cross-linked polymerallows water to diffuse in and out of the contact lens body to thecavity from an external surface of the body. The contact lens bodycomprises an anterior surface and a posterior surface. The posteriorsurface, anterior surface, and cavity are shaped to correct vision withsaid cavity in equilibrium with tear fluid of the eye.

In another aspect, an erodible insert for use in manufacturing a softcontact lens is provided. The insert comprises an erodible materialcomposed of a first material configured to dissolve and pass throughchannels of a hydrogel contact lens and a second material configuredwith one or more of particle size or solubility to remain within acavity formed by dissolution of the first material.

In another aspect, an erodible insert for use in manufacturing a softcontact lens is provided. The insert comprises an erodible materialcomposed of a first material configured to dissolve and pass throughchannels of a hydrogel contact lens and a second material configuredwith one or more of particle size or solubility to remain within acavity formed by dissolution of the first material. The second materialcomprises an amount sufficient to provide an osmolality of the cavitywithin a range from about 200 milli osmols to about 290 milli osmolswhen the first material has passed through the channels.

In another aspect, an erodible insert for use in manufacturing a softcontact lens is provided. The insert comprises an erodible materialcomposed of a first polymer material configured to dissolve and passthrough channels of a hydrogel contact lens and a second less solublepolymer material configured to remain within a cavity formed bydissolution of the first material. The first polymer material comprisesa water soluble material and the second polymer material comprises awater insoluble material.

In another aspect, an erodible insert for use in manufacturing a softcontact lens is provided. The insert comprises an erodible materialcomposed of a first polymer material comprising a first amount ofacetate and configured to dissolve and pass through channels of ahydrogel contact lens and a second less soluble polymer materialcomprising a greater amount of acetate to remain within a cavity formedby dissolution of the first material.

In another aspect, an erodible insert for use in manufacturing a softcontact lens is provided. The insert comprises an erodible materialcomposed of a first water soluble polymer material comprising a firstmolecular weight and configured to dissolve and pass through channels ofa hydrogel contact lens and a second polymer material comprising asecond molecular weight greater the first molecular weight to remainwithin a cavity formed by dissolution of the first material.

In another aspect, an erodible insert for use in manufacturing a softcontact lens is provided. The insert comprises an erodible materialshaped to have front and back surfaces each having curvaturecorresponding to one or more surfaces of the soft contact lens, acircular region shaped to define an inner optical chamber, an outerregion, and an extension extending between the inner region and theouter region, the extension comprising a maximum dimension across sizedless than a diameter of the circular region.

In another aspect, an erodible insert for use in manufacturing a softcontact lens is provided. The insert comprises an erodible materialshaped to have front and back surfaces each having curvaturecorresponding to one or more surfaces of the soft contact lens, thefront and back surfaces sufficiently smooth to impart optical quality tocorrect vision with the contact lens, a circular region shaped to definean inner optical chamber, an outer region, and an extension extendingbetween the inner region and the outer region, the extension comprisinga maximum cross-sectional dimension sized less than a diameter of thecircular region, the outer region comprising a maximum dimension acrosssized greater than the maximum cross-sectional dimension of theextension.

In many embodiments, the insert may comprise a biocompatible watersoluble polymer. The biocompatible water soluble polymer may compriseone or more of polyvinyl alcohol, polyvinyl acetate, polyethylene oxide,propylene oxide, copolymer of ethylene and propylene oxides (Pluronicacids), poly vinyl pyrollidone, polyethylene imine, polyacrylamide,polysaccharide, polyethylene glycol (PEG) in the molecular weight rangeof about 600 g/mol to about 6000 g/mol, hydrophilic ionic polyacrylates,polymethacrylates, or copolymers of hydrophilic ionic polyacrylates andpolymethacrylates.

In many embodiments, the cavity may have been formed from an insert withan optically smooth surface. Upper and lower portions of the lens bodydefining the optical chamber may comprise optically smooth surfaces inorder to allow vision correction.

In many embodiments, the cavity may have been formed from an insert withan optically smooth surface. Upper and lower portions of the lens bodydefining the optical chamber may comprise optically smooth surfaces inorder to allow vision correction. The surfaces may have an RMS value orabout 50 nm or less.

In many embodiments, the cavity may comprise particles contained withinsaid cavity.

In many embodiments, the cavity may comprise particles comprisingdimensions greater than dimensions of channels of a hydrogel polymerdefining the cavity to contain the particles within the cavity.

In many embodiments, the cavity may comprise one or more of soluble,partially soluble or insoluble particles contained within the cavity.The particles may comprise dimensions greater than dimensions ofchannels of a hydrogel polymer defining the cavity to contain theparticles within the cavity.

In many embodiments, the cavity may comprise polymer comprising acetate.

In many embodiments, the cavity may comprise a refractive indexgradient. The refractive index gradient may comprise a greater index ofrefraction near the boundary of the cavity and a lesser index ofrefraction in an interior of the cavity away from the boundary.

In many embodiments, the insert may comprise hydrogen bonds between atleast a portion of the insert with the hydrogel contact lens material inorder to provide the cavity with a refractive index gradient. Therefractive index gradient may comprise a greater index of refractionnear the boundary of the cavity and a lesser index of refraction in theinterior of the cavity away from the boundary.

In many embodiments, the cavity insert may comprise a tapered edge inorder to inhibit prism related to an abrupt change in refractive indexnear a boundary of the cavity formed in the hydrogel contact lensmaterial.

In many embodiments, the cavity may comprise solubilized polymerparticles having insoluble pendant groups. The hydrogel may comprisechannels made of a hydrophilic material to allow water to pass whenhydrated while the insoluble pendant groups maintain the polymerparticles within said chamber when hydrated.

In many embodiments, the hydrogel polymer enclosing said cavity may beconfigured to replace at least a portion of the liquid contained withinthe cavity with tear fluid when placed on the eye of a wearer.

In many embodiments, the hydrogel polymer enclosing the cavity may beconfigured to release liquid from within the cavity to an exterior ofthe soft contact lens to provide the liquid to the eye.

In many embodiments, the material within the cavity may comprise anindex of refraction less than an index of refraction of the hydrogelmaterial encapsulating the cavity when hydrated. The cavity may beshaped to add negative optical power to the lens with the materialcontained therein.

In many embodiments, the inner cavity providing optical correction maybe encapsulated on an anterior side and a posterior side with thecontact lens body within an optically used portion of the cavity. Theanterior side of the contact lens body may comprise an anteriorthickness and the posterior side may comprise a posterior thickness. Theanterior thickness may be less than the posterior thickness in order tofacilitate deflection of the anterior surface of the lens when thecontact lens comprises a presbyopia correcting near vision configurationwith inflation and increased optical power of the inner portion of thechamber.

In many embodiments, the inner cavity providing optical correction maybe encapsulated on an anterior side and a posterior side with thecontact lens body within an optically used portion of the cavity. Theanterior side of the contact lens body may comprise an anteriorthickness and the posterior side may comprise a posterior thickness. Theanterior thickness may be less than the posterior thickness and theanterior and posterior surfaces may deflect with inflation of theoptical inner portion of the chamber. The anterior surface may deflectmore than said posterior surface with inflation to correct presbyopia.

In many embodiments, the inner cavity providing optical correction maybe encapsulated on an anterior side and a posterior side with thecontact lens body within an optically used portion of the cavity. Theanterior side of the contact lens body may comprise an anteriorthickness and the posterior side comprises a posterior thickness. Theanterior thickness may be at least about 50 um.

In many embodiments, the inner cavity providing optical correction maybe encapsulated on an anterior side and a posterior side with thecontact lens body within an optically used portion of the cavity. Theanterior side of the contact lens body may comprise an anteriorthickness and the posterior side comprises a posterior thickness. Theanterior thickness may be no more than about 100 um.

In many embodiments, the inner cavity providing optical correction maybe encapsulated on an anterior side and a posterior side with thecontact lens body within an optically used portion of the cavity. Theanterior side of the contact lens body may comprise an anteriorthickness and the posterior side may comprise a posterior thickness. Theanterior thickness may be within a range defined between any two of thefollowing values: about 10 microns, about 25 microns, about 50 microns,about 100 microns, about 150 microns, and 200 microns.

In many embodiments, the inner cavity providing optical correction maybe encapsulated on an anterior side and a posterior side with thecontact lens body within an optically used portion of the cavity. Theanterior side of the contact lens body may comprise an anteriorthickness and the posterior side may comprise a posterior thickness. Theposterior thickness may be at least about 100 um.

In many embodiments, the inner cavity providing optical correction maybe encapsulated on an anterior side and a posterior side with thecontact lens body within an optically used portion of the cavity. Theanterior side of the contact lens body may comprise an anteriorthickness and the posterior side may comprise a posterior thickness. Theposterior thickness may be no more than about 200 um.

In many embodiments, channels of a material of the hydrogel contact lensbody may be sized to allow a disinfectant to flow from the chamber tothe eye and to inhibit bacteria from entering the chamber from anexterior of the lens body into the chamber.

In many embodiments, the cavity may comprise a different refractiveindex than a hydrogel material of the contact lens body encapsulatingthe cavity.

In many embodiments, the cavity may comprise a different refractiveindex than a hydrogel material of the contact lens body encapsulatingthe cavity. The refractive index of the cavity may be different by atleast about 0.03 from the refractive index of the material encapsulatingthe cavity.

In many embodiments, the cavity may comprise a different refractiveindex than a hydrogel material of the contact lens body encapsulatingthe cavity. The refractive index of the cavity may be different by atleast about 0.05 from the refractive index of the material encapsulatingthe cavity.

In many embodiments, the cavity may comprise a different refractiveindex than a hydrogel material of the contact lens body encapsulatingthe cavity. The refractive index of the cavity may be different by atleast about 0.10 from the refractive index of the material encapsulatingthe cavity.

In many embodiments, the cavity may comprise a similar refractive indexas a hydrogel material of the contact lens body encapsulating thecavity. The refractive index of the cavity may be within about 0.03 ofthe refractive index of the material encapsulating the cavity.

In many embodiments, the cavity may comprise a similar refractive indexas a hydrogel material of the contact lens body encapsulating thecavity. The refractive index of the cavity may be within about 0.05 ofthe refractive index of the material encapsulating the cavity.

In many embodiments, the cavity may comprise a negative optical powerrefracting light in a far vision configuration. Anterior and posteriorsurfaces of said lens body may each be configured with a radius ofcurvature with the cavity to provide far vision correction.

In many embodiments, the cavity may comprise an inner optical chamber toprovide optical correction and a first outer chamber and a second outerchamber connected with one or more channels extending there between. Thefirst outer chamber may be located inferior to the inner chamber. Thefirst outer chamber may comprise an amount of fluid to provideintermediate vision correction to the inner optical chamber. The secondouter chamber may comprise an amount of fluid to provide near visioncorrection when combined with fluid from the first outer chamber. Thefirst outer chamber may be located inferiorly to the second outerchamber to engage the first outer chamber with the eyelid to provideintermediate vision correction and to engage with the eyelid both thefirst outer chamber and the second outer chamber to provide near visioncorrection.

In many embodiments, the liquid contained within the cavity may comprisean osmolality within a range from about 200 (two hundred) to about 290mOsmol/L (two hundred ninety milli osmols per liter).

In many embodiments, the liquid contained within the cavity may comprisean osmolality within a range from about 250 to about 290 mOsmol/L (twohundred ninety milli osmols per liter).

In many embodiments, the liquid contained within the cavity may compriseparticles composed of a hydrophobic material to inhibit release of theparticles through the hydrogel material encapsulating the cavity.

In many embodiments, the liquid contained within the cavity may compriseparticles composed of a hydrophobic material comprising acetate toinhibit release of the particles through the hydrogel materialencapsulating the cavity.

In many embodiments, the lens body may comprise side chains of polymerextending into said cavity in order to provide a gradient refractiveindex.

In many embodiments, the lens body may comprise side chains of polymercomprising acetate extending into the cavity in order to provide agradient refractive index.

In many embodiments, an interface of the cavity with the contact lensbody may comprise a HEMA hydrophilically bonded with polyvinyl alcohol(PVA).

In many embodiments, the insert may comprise polyvinyl alcohol (PVA) andacetate (Ac).

In many embodiments, the insert may comprise a copolymer of polyvinylalcohol (PVA) and polyvinyl acetate (PVAc).

In many embodiments, the insert may comprise a copolymer of polyvinylalcohol (PVA) and polyvinyl acetate (PVAc) with vinyl acetate groupsinterspersed among vinyl alcohol groups.

In many embodiments, the insert may comprise a solid material composed aplurality of polymer chains comprising of polyvinyl alcohol (PVA) andvinyl acetate (VAc) along said each of the plurality of chains.

In many embodiments, the insert may comprise a solid material composed aplurality of polymer chains, the polymer chains comprising vinyl alcohol(PVA) and vinyl acetate (VAc) along said each of the plurality ofchains. Each of the plurality of chains may have from about 1000 toabout 1500 pendant groups comprising a combination of alcohol andacetate.

In many embodiments, the insert may comprise a solid material composed aplurality of polymer chains comprising of polyvinyl alcohol (PVA) andpoly vinyl acetate (VAc) along said each of the plurality of chains.Each of the plurality of chains may be configured to erode from theinsert. The plurality of polymer chains may have an average molecularweight of within a range from about 50 kD to about 150 kD.

In many embodiments, the insert may comprise a solid material composed aplurality of polymer chains comprising of polyvinyl alcohol (PVA) andpoly vinyl acetate (VAc) along said each of the plurality of chains.Each of the plurality of chains may be configured to separate from otherchains and erode from the insert. The plurality of polymer chains mayhave an average molecular weight of within a range from about 50 kD toabout 110 kD.

In many embodiments, the insert may comprise a solid material composed aplurality of polymer chains comprising of polyvinyl alcohol (PVA) andpoly vinyl acetate (VAc) along said each of the plurality of chains.Each of the plurality of chains may be configured to separate from otherchains and erode from the insert. The plurality of polymer chains mayhave an average molecular weight of within a range from about 100 kD toabout 110 kD.

In many embodiments, the insert may comprise a solid material composedof a plurality of polymer chains comprising of polyvinyl alcohol (PVA)and polyvinyl acetate (PVAc) along said each of the plurality of chains.Each of the polymer chains may comprise PVAc within a range from about0.05% to about 10% and PVA within a range from about 90% to about 99.5%.The vinyl acetate groups may be interspersed among vinyl alcohol groups.

In many embodiments, the insert may comprise a solid material composedof polyvinyl alcohol (PVA) polymer and polyvinyl acetate (PVAc). ThePVAc may comprise an amount by weight of the material within a rangefrom about 1% to about 20%. The PVA may comprise an amount by weightwithin a range from about 99% to about 80%.

In many embodiments, the cavity may comprise a therapeutic agentselected from the group consisting of: anti-infectives, including,without limitation, antibiotics, antivirals, and antifungals;antiallergenic agents and mast cell stabilizers; steroidal andnon-steroidal anti-inflammatory agents; cyclooxygenase inhibitors,including, without limitation, Cox I and Cox II inhibitors; combinationsof anti-infective and anti-inflammatory agents; decongestants;anti-glaucoma agents, including, without limitation, adrenergics,β-adrenergic blocking agents, α-adrenergic agonists, parasypathomimeticagents, cholinesterase inhibitors, carbonic anhydrase inhibitors, andprostaglandins; combinations of anti-glaucoma agents; antioxidants;nutritional supplements; drugs for the treatment of cystoid macularedema including, without limitation, non-steroidal anti-inflammatoryagents; drugs for the treatment of ARMD, including, without limitation,angiogenesis inhibitors and nutritional supplements; drugs for thetreatment of herpetic infections and CMV ocular infections; drugs forthe treatment of proliferative vitreoretinopathy including, withoutlimitation, antimetabolites and fibrinolytics; wound modulating agents,including, without limitation, growth factors; antimetabolites;neuroprotective drugs, including, without limitation, eliprodil; andangiostatic steroids for the treatment of diseases or conditions ofposterior segment, including, without limitation, ARMD, CNV,retinopathies, retinitis, uveitis, macular edema, and glaucoma.

In many embodiments, the insert may comprise a material capable of beingbent to a radius of curvature within a range from about 5 mm to about 1meter. The material may optionally comprise an elastic material.

In many embodiments, the cavity may comprise one or more channels tofacilitate removal of the residual insert material. The one or morechannels may be formed by puncturing the lens body with a syringe,needle, or laser. Alternatively or in combination, the one or morechannels may be formed by chemical erosion of a pre-determined portionof the lens body. Alternatively or in combination, the one or morechannels may be formed by erosion of the insert. The insert may compriseone or more protrusions correspondingly shaped to the one or morechannels. Alternatively or in combination, the one or more channels maybe formed outside of the optical zone to reduce visual aberrations ofthe lens. Alternatively or in combination, the one or more channels maybe formed towards an outer edge of the lens, the posterior surface ofthe lens, or the anterior surface of the lens. Alternatively or incombination, the one or more channels may be one or more of filled in,plugged, sealed, sealed with polymer comprising a polymer of the contactlens, or welded, following erosion of the insert and formation of thecavity.

In many embodiments, the insert may comprise one or more protrusionsshaped so as to define one or more channels in the lens body from thecavity to one or more external sides of the lens after formation of thelens around the insert and erosion of the insert.

In many embodiments, the cavity may comprise residual insert material.An inner surface of the cavity may comprise a residual surface structurecomprising the residual insert material. The residual surface structuremay be optically smooth. The residual surface structure may optionallycomprise no visually perceptible artifacts.

In many embodiments, the insert may have a thickness within a rangedefined between any two of the following values: about 0.5 microns,about 15 microns, about 50 microns, about 75 microns and about 100microns.

In many embodiments, the insert may have a thickness of greater thanabout 100 microns.

In many embodiments, the insert may comprise an insert material that isselected from the group consisting of dissolvable, erodible, degradable,and solulizable, by an aqueous solution, alcohol, or solvent.

In many embodiments, the insert may comprise an insert material that isselected from the group consisting of moldable, extrudable, andphoto-curable.

In many embodiments, the insert material may comprise material selectedfrom the group consisting of a sugar or sugar alcohol. The insertmaterial may comprise a sugar. The sugar may be selected from the groupconsisting of a mono-saccharide, di-saccharide, and poly-saccharide.Alternatively or in combination, the sugar may be selected from thegroup consisting of fructose, galactose, glucose, glyceraldehyde,lactose, maltose, ribose, sucrose, cellulose, and methylcellulose.Alternatively or in combination, the insert material may comprise asugar alcohol. The sugar alcohol may be selected from the groupconsisting of arabitol, D-sorbitol, erythritol, fucitol, galactiol,glycerol, iditol, inositol, isomalt, lactitol, maltotetraitol, maltitol,maltotritol, mannitol, myo-inositol, polyglycitol, ribitol, sorbitol,threitol, and xylitol.

In many embodiments, the insert material may comprise a materialselected from the group consisting of dimethyl sulfoxide (DMSO),N-vinylpyrrolidone (NVP), polyethylene glycol (PEG), poly sodiummethacrylate, MethocelTM E6, polyvinyl alcohol (PVA), polyvinyl acetate(PVAc), and a copolymer of PVA and PVAc.

In many embodiments, the insert material may comprise a materialselected from the group consisting of sodium chloride, sodium carbonate,and potassium chloride.

In many embodiments, the lens may be formed by one or more of casting,extrusion, molding, or lamination.

In many embodiments, the lens may comprise a material selected from thegroup consisting of acofilcon A, acofilcon B, alfafilcon A, altraficonA, atlafilcon A, balafilcon A, bufilcon A, comfilcon A, crofilcon,deltafilcon A, dimefilcon A, droxifilcon A, efrofilcon A, enfilcon,epsifilcon A, etafilcon A, focofilcon A, galyfilcon A, heflicon A,heflicon B, hefilcon C, hilafilcon A, hilafilcon B, hioxifilcon A,hioxifilcon B, hioxifilcon D, isofilcon , lidofilcon A, lidofilcon B,lotrafilcon A, lotrafilcon B, mafilcon, methafilcon A, methafilcon B,narafilcon B, nelfilcon A, nescofilcon A, netrafilcon A, ocufilcon A,ocufilcon B, ocufilcon C, ocufilcon D, ocufilcon E, ocufilcon F, ofilconA, omafilcon A, phemfilcon, phemfilcon A, polymacon, perfilcon A,samfilcon A, scafilcon A, senofilcon A, sifilcon A, surfilcon A,teflicon, tetrafilcon A, tetrafilcon B, vasurfilcon A, vilfilcon A, andxylofilcon A.

In many embodiments, the cavity may be defined by the interior walls ofthe lens body.

In many embodiments, the inner cavity providing optical correction maybe encapsulated on an anterior side and a posterior side with thecontact lens body within an optically used portion of the cavity. Theanterior side of the contact lens body may deflect when the contact lenscomprises a presbyopia correcting near vision configuration withinflation providing increased optical power of the inner portion of thecavity. The deflection may provide uniform changes in optical power ofthe inner portion of the cavity.

In many embodiments, the inner cavity providing optical correction maybe encapsulated on an anterior side and a posterior side with thecontact lens body within an optically used portion of the cavity. Theanterior side of the contact lens body may deflect when the contact lenscomprises a presbyopia correcting near vision configuration withinflation and may provide increased optical power of the inner portionof the cavity. The deflection may provide uniform changes in opticalpower of the inner portion of the cavity.

In many embodiments, the contact lens may comprise a multifocal profilewith distinct regions of differing optical power. The contact lens mayoptionally comprise the multifocal profile in a near visionconfiguration.

In many embodiments, the contact lens may comprise a multifocal profilewith a continuously varying region of optical power. The contact lensmay optionally comprise the multifocal profile in a near visionconfiguration.

In many embodiments, the cavity may comprise cross-linked insertmaterial. The cavity may comprise insert material cross-linked to thelens body and extending from the lens body into said cavity.Alternatively or in combination, the cavity may comprise insert materialcross-linked to the lens body and extending from a surface of the lensbody into said cavity to another surface of the lens body.

In many embodiments, the insert may comprise a UV blocker or absorber toprevent or modify the extent or location of insert cross-linking withinthe cavity. Alternatively or in combination, the insert may comprise aninsert material which does not cross-link under exposure to UV light.

In many embodiments, the cavity may comprise a therapeutic agent. Thetherapeutic agent may have a half-life within a range of about 1 day toabout 7 days. The hydrogel polymer enclosing the cavity may beconfigured to release liquid containing a therapeutic agent from withinthe cavity to an exterior of the soft contact lens to provide thetherapeutic agent to the eye. Alternatively or in combination, theinsert may comprise a therapeutic agent which remains in the cavityafter the insert has dissolved. Alternatively or in combination, thecavity may be in equilibrium with an external solution comprising atherapeutic agent such that the cavity comprises said therapeutic agent.

In many embodiments, an amount of therapeutic agent within the cavitymay be controlled by concentration, size of the therapeutic agent,molecular weight of the therapeutic agent, temperature, pore size of thelens body, thickness of the posterior side of the lens, or thickness ofthe anterior side of the lens.

In many embodiments, the posterior side of the lens may comprise athickness within a range defined between any two of the followingvalues: about 10 microns, about 25 microns, about 50 microns and about100 microns, and about 200 microns.

In many embodiments, the therapeutic agent may comprise a molecularweight within a range of about 18 Daltons to about 10 kilo Daltons.

In many embodiments, the anterior side of the lens may comprise athickness within a range of defined between any two of the followingvalues: about 10 microns, about 25 microns, about 50 microns, about 100microns, about 150 microns, and 200 microns

In many embodiments, the cavity may comprise a therapeutic amount of atherapeutic agent. The therapeutic amount may change the refractiveindex of the cavity within a range of about 0.01 to about 0.02 such thatvision is not significantly altered by the presence of the therapeuticagent in the cavity.

In many embodiments, the cavity may comprise a therapeutic agent. Thecavity may be located near a posterior lens surface, near an anteriorlens surface, or near the center of the lens to control release of thetherapeutic agent to the eye. Alternatively or in combination, thecavity may be located outside the optical zone.

In many embodiments, the soft contact lens may comprise a first cavitylocated within the optical zone of the lens and a second cavity locatedoutside the optical zone. The first cavity may provide opticalcorrection to the lens when deflected. The second cavity may comprise atherapeutic agent and provide the therapeutic agent to the eye throughthe lens body.

In another aspect a method is provided. The method comprises providingany of the contact lens embodiments described herein. Alternatively orin combination, the method comprises providing any of the erodibleinsert embodiments described herein.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1A shows a cross-sectional view of a contact lens comprising aninternal cavity, in accordance with embodiments;

FIG. 1B shows an enlarged section of the contact lens as in FIG. 1A, inaccordance with embodiments;

FIG. 2 shows a cross-sectional view of a contact lens in sterilepackaging with cavity in equilibrium with the fluid in which the lens inpackaged, in accordance with embodiments;

FIG. 3A shows a cross-sectional view of a curved insert comprising asoluble polymer, in accordance with embodiments;

FIG. 3B shows a top view of a curved insert comprising a soluble polymeras in FIG. 3A;

FIG. 4 shows a contact lens cavity following dissolution of insert, inaccordance with embodiments;

FIG. 5 shows a contour map of a lens due to inflation of the opticalchamber of the cavity by simulated action of lower eyelid on the contactlens, in accordance with embodiments;

FIG. 6 shows a stabilized contact lens, in accordance with embodiments;

FIG. 7 shows a contact lens comprising a sensor wherein at least aportion of the sensor is located within the cavity, in accordance withembodiments;

FIG. 8 shows a method of manufacturing a lens comprising a cavity formedby dissolving an insert, in accordance with embodiments;

FIG. 9A shows a cross-sectional view of a contact lens comprising aninternal cavity comprising residual insert material, in accordance withembodiments;

FIG. 9B shows an erodible insert material comprising a copolymer ofpolyvinyl alcohol and polyvinyl acetate, in accordance with embodiments;

FIG. 10 shows a contact lens with a single peripheral reservoir, inaccordance with embodiments;

FIG. 11 shows a contact lens with a progressive peripheral reservoir, inaccordance with embodiments;

FIG. 12 shows a contact lens with two peripheral reservoirs, inaccordance with embodiments;

FIG. 13A shows a cross-sectional view of a contact lens comprising aninternal cavity and hole, in accordance with embodiments;

FIG. 13B shows a cross-sectional view of an insert comprising aprotrusion, in accordance with embodiments;

FIG. 13C shows a cross-sectional view of a contact lens comprising aninternal cavity and filled-in hole, in accordance with embodiments;

FIG. 14 shows a cross-sectional view of a contact lens comprising aninternal cavity and comprising a multifocal lens, in accordance withembodiments;

FIG. 15 shows a cross-sectional view of a contact lens comprising aninternal cavity with cross-linked material, in accordance withembodiments;

FIG. 16 shows a cross-sectional view of a contact lens comprising aninternal cavity with a drug contained therein, in accordance withembodiments;

FIG. 17 shows a cross-sectional view of a contact lens comprising aninternal cavity close to the posterior of the lens with a drug containedtherein, in accordance with embodiments;

FIG. 18 shows a cross-sectional view of a contact lens comprising aninternal cavity close to the anterior of the lens with a drug containedtherein, in accordance with embodiments;

FIG. 19 shows a cross-sectional view of a contact lens comprising aninternal cavity outside the optical zone with a drug contained therein,in accordance with embodiments;

FIG. 20 shows simulated results of lens power as a function of theposterior radius of curvature of a cavity, in accordance withembodiments;

FIG. 21 shows simulated results of lens power as a function of cavityposition within the lens, in accordance with embodiments;

FIGS. 22A-22B show casting cups used to cast an accommodating contactlens, in accordance with embodiments;

FIG. 23A shows an accommodating contact lens after 2 hours of hydrationin 0.9% saline and 1.5 hours of sonication, in accordance withembodiments;

FIG. 23B shows an accommodating contact lens after hydrating overnight,in accordance with embodiments;

FIG. 24 shows an accommodating soft contact lens with an embedded cavityunder bright-field microscopy, in accordance with embodiments;

FIG. 25 shows an accommodating soft contact lens comprising a cavity oneye, in accordance with embodiments;

FIG. 26 shows an accommodating soft contact lens comprising an inkedcavity on eye, in accordance with embodiments;

FIG. 27 shows a lens power measurement test for an accommodating softcontact lens, in accordance with embodiments;

FIG. 28A shows the accommodating soft contact lens of FIG. 26 on eye, inaccordance with embodiments;

FIG. 28B shows an optical coherence tomography (OCT) cross-section ofthe contact lens of FIG. 28A, in accordance with embodiments;

FIG. 29 shows an accommodating soft contact lens comprising a cavitywith central bulging on eye, in accordance with embodiments;

FIG. 30A shows the accommodating soft contact lens of FIG. 29 on eye, inaccordance with embodiments;

FIG. 30B shows an OCT cross-section of the contact lens of FIG. 30A, inaccordance with embodiments;

FIG. 31 shows a method of manufacturing a contact lens comprising acavity, in accordance with embodiments;

FIG. 32 shows a lens comprising a low molecular weight dye prior toincubation in an extraction solution, in accordance with embodiments;

FIG. 33 shows the lens of FIG. 32 after 24 hours incubation in anextraction solution, in accordance with embodiments;

FIG. 34A a lens comprising a low molecular weight dye prior toincubation in an extraction solution, in accordance with embodiments;

FIG. 34B shows the lens of FIG. 34A after 5 hours incubation in anextraction solution, in accordance with embodiments;

FIG. 34C shows the lens of FIG. 34A after 5 hours incubation in anextraction solution, in accordance with embodiments;

FIG. 34D a lens comprising a low molecular weight dye prior toincubation in an extraction solution, in accordance with embodiments;

FIG. 34E shows the lens of FIG. 34D after 5 hours incubation in anextraction solution, in accordance with embodiments;

FIG. 34F shows the lens of FIG. 34D after 5 hours incubation in anextraction solution, in accordance with embodiments;

FIG. 35A shows a sucrose film generated using a cast-free method, inaccordance with embodiments;

FIG. 35B shows a sucrose film generated using a cast-free method, inaccordance with embodiments;

FIG. 35C shows a free-standing sucrose film generated using a cast-freemethod, in accordance with embodiments;

FIG. 36A shows the flexibility of a sucrose insert film, in accordancewith embodiments;

FIG. 36B shows the flexibility of a glucose insert film, in accordancewith embodiments;

FIG. 36C shows the flexibility of an isomalt insert film, in accordancewith embodiments;

FIG. 36D shows the results of cavity formation after diffusion of asucrose insert, in accordance with embodiments;

FIG. 36E shows the results of cavity formation after diffusion of aglucose insert, in accordance with embodiments;

FIG. 36F shows the results of cavity formation after diffusion of anisomalt insert, in accordance with embodiments;

FIG. 37A shows an insert made of sodium chloride, in accordance withembodiments;

FIG. 37B shows the results of cavity formation after diffusion of asodium chloride insert, in accordance with embodiments;

FIG. 37C shows the results of cavity formation after diffusion of asodium chloride insert, in accordance with embodiments; and

FIG. 37D shows the results of cavity formation after diffusion of asodium chloride insert, in accordance with embodiments.

DETAILED DESCRIPTION OF THE INVENTION

The cavity lenses disclosed herein are well suited for combination withmany prior art lenses, such as contact lenses. The cavity lens can becombined with accommodating soft contact lenses or accommodatingintraocular lenses, for example.

A soft contact lens comprising a cavity filled with a liquid functionsas a dynamic accommodating contact lens that provides the requiredrefractive correction to presbyopes at all distances from far to near.The cavity comprises an optical chamber aligned with the optical centerof the lens itself, and a peripheral chamber positioned vertically belowthe optical chamber and connected to the optical chamber by means of achannel. When fitted on an eye, the optical chamber of the cavity ispositioned over the center of the pupil while the peripheral chamber ispositioned to interact with the lower eyelid at down-gaze. Pressure fromthe lower eyelid forces fluid from the peripheral chamber into theoptical chamber, causing the cavity to inflate and push out the anteriorsurface of the contact lens, thus causing its curvature to steepen.Consequently, the center of the lens undergoes an increase in plus powerto correct near vision that persists as long as the peripheral chamberof the cavity remains compressed by the lower eyelid. The design andprocess of fabrication of such a soft contact lens is disclosed herein.

The accommodating soft contact lenses described in the following patentapplications are well suited for combination with the cavity contactaccommodating contact lenses described herein: WO/2015/095891, entitled“FLUIDIC MODULE FOR ACCOMODATING SOFT CONTACT LENS”, and WO/2014/117173,entitled “ACCOMODATING SOFT CONTACT LENS”, the entire disclosures ofwhich are incorporated herein by reference.

The inventors have designed and fabricated a spherical soft contact lenscontaining an embedded cavity that functions as an accommodating contactlens. The cavity may have a clearly defined circular optical chamber anda lower peripheral chamber connected to the optical chamber with achannel. The cavity is formed by placing an insert made of a watersoluble polymer of appropriate shape and thickness inside a mold cavityused to form the contact lens. The lens is hydrated after being cured.The insert dissolves in the hydration medium, typically physiologicalsaline leaving a cavity filled with saline. Preferably, a low expansionpolymer is used to form the contact lens, so that the cavity does notchange in size as the lens is hydrated. The accommodating contact lenscan be configured in many ways, including a monofocal aspheric design, amonofocal, and stabilized lenses for enhanced rotational stability. Thepresent inventors have manufactured lenses and conducted experiments asdescribed herein.

As used herein, “PVA” refers to poly vinyl alcohol.

As used herein, “PVAc” refers to poly vinyl acetate.

FIG. 1A shows a cross-sectional view of a hydrogel contact lens 100comprising an internal cavity 110. Although a contact lens is shown, thebody with the cavity could be many things besides or in addition to thecontact lens. Cavity 110 may be formed by the dissolution of a solidmaterial, for example an insert, thereby giving the cavity 110 a shapeprofile and structure corresponding to that of the dissolved insert.Lens 100 comprises a lens material 120 of sufficient stiffness so as toretain the shape of a dissolvable insert following hydration and insertdissolution. The inner surface of cavity 110 may comprise an opticallysmooth surface through which light may pass in order to correct vision.Cavity 110 may comprise one or more internal structures formed bydissolving an erodible material. One embodiment of a dissolvable insertis described in greater detail in FIG. 3. The lens cavity 110 may beshaped in numerous ways, as defined by the shaped of the dissolvableinsert, allowing for ready fabrication of a cavity 110 within thecontact lens 100.

FIG. 1B shows an enlarged section of contact lens 100 depicting cavity110 with a portion 130 of contact lens body 120. Cavity 110 is filledwith a volume of cavity liquid 112, comprising for example residualdissolved insert material or the fluid used to hydrate the lens 100,within a range from about 14 to 54. The residual insert material 112 mayhave a molecular weight within one or more of many ranges such that theresidual insert material 112 is able to diffuse through the polymer ofthe contact lens body 120. The range of molecular weights can be fromabout 3 kDaltons (kD) to about 10 kD, and can be from about 3 kD toabout 7 kD. The upper contact lens surface 132 which forms the base ofcavity 110 comprises exposed polymer 134 in contact with cavity liquid112. The lower contact lens surface 136 comprises a posterior lenssurface which may contact the eye.

FIG. 2 shows a cross-sectional view of a contact lens 100 in sterilepackaging 200 with the cavity 110 in equilibrium 202 with the fluid 204in which the lens is packaged. The contact lens 100 may be immersed in asterile fluid 204 within the sterile packaging. Cavity 110 is filledwith a liquid 112 and is permeable to the aqueous fluid 204 in which thelens is packaged, such that the cavity 110 is in equilibrium 202 withthe fluid 204 outside the lens body 120. At least a portion of the fluid204 may diffuse into cavity 110. When placed on the eye, the contactlens 100 permeability allows the lens 100 to hydrate the eye with cavityliquid 112.

FIG. 3A shows a cross-sectional view of an insert 140 made of a solublepolymer. The insert 140 comprises a three-dimensional shape profile ofsubstantially uniform thickness which, after dissolution, corresponds tothe shape of the cavity 110. The insert 140 may comprise a materialhaving a molecular weight of at least 3 kDaltons so as to add sufficientstiffness to the material to retain a given shape at a processingtemperature that may range from 10° C. to 45° C. Insert 140 preferablycomprises a low expansion polymer, such that hydration of the lens doesnot alter the size of the cavity 110. The upper surface 142 and lowersurface 144 of an insert 140 may also have a curvature corresponding tothe curvature of a mold used to define a base curvature of the lens 100.One example of such a mold is shown in FIGS. 22A-22B.

The contact lens material may comprise a low amount of expansion uponhydration. The lens material can be cured in a mold with an insert andthen hydrated as described herein. Low expansion hydrogel materials aredescribed in U.S. Pat. No. 62/254,048, filed on 11 Nov. 2015, entitled“SOFT CONTACT LENS MATERIAL WITH LOW VOLUMETRIC EXPANSION UPONHYDRATION”, the entire disclosure of which is incorporated herein byreference.

FIG. 3B shows a top view of an insert 140 as in FIG. 3A. Insert 140 maycomprise a shape with a portion 146 corresponding to an inner opticalchamber of a lens 100, a portion 148 corresponding to a lower chamber oflens 100, and a portion 147 corresponding to a channel extending betweenthe chambers. The diameter 149 of the portion 147 corresponding to saidchannel may be within a range of about 0.2 mm to 2 mm. When the insert140 dissolves inside the lens body 120, the resulting cavity 110 canretain the shape profile of the insert 140.

The insert 140 can be sized and shaped in many ways suitable for theapplication of the body comprising the polymer. The insert may comprisea three dimensional shape profile, for example. The insert 140 can beformed in many ways, for example with three dimensional printing. Thethree dimensional shape profile may comprise an outer boundary definingthe outer boundary of the cavity 110. The shape profile may comprise oneor more curved surfaces corresponding to one or more surfaces of thecontact lens, for example corresponding to the lower base curvature ofthe contact lens. The insert can be fabricated in many ways, for examplewith three dimensional printing of the insert material.

FIG. 4 shows a contact lens 100 and cavity 110 following dissolution ofinsert 140. Upon hydration of the contact lens 100, insert 140, whichmay have a shape profile as depicted in FIG. 3B, dissolves to form acavity 110 corresponding to the shape of the dissolved insert 140.Diffusion of the dissolved insert material away from the cavity 110 mayinhibit osmotic pressure and expansion of cavity 110 as the insert 140dissolves, such that the structural integrity of the lens body 120 andcavity 110 may be maintained. The insert material can diffuse throughthe polymer material of the body at a sufficient rate to inhibit abuild-up of osmotic pressure that could otherwise compromise thestructural integrity of the soft lens material and shape of theresulting cavity.

The cavity 110 may be shaped to correct vision when in equilibrium withtear fluid of the eye. The cavity 110 may comprise an inner opticalchamber 114 which corresponds in shape and structure to portion 146 ofinsert 140, a lower chamber 116 which corresponds to portion 148 ofinsert 140, and a channel 118 extending there between which correspondsto portion 147 of insert 140. The contact lens 100 may also comprise oneor more hinges coupled to inner optical chamber 114 and lower chamber116. Lower chamber 116 comprises a liquid reservoir in fluidcommunication with inner optical chamber 114 via channel 118.

Inner optical chamber 114 and lower chamber 116 may be configured inmany ways.

Cavity 110 may provide hydration to the eye with release of water,saline, or other fluid through the lens body 120 in order to hydrate theeye.

The lens body 120 may comprise a polymer comprising channels sized topermit diffusion of water between the cavity 110 and outside the lensbody and also sized to prevent bacteria from entering the cavity 110from outside the lens body.

Cavity 110 may comprise a drug to treat the eye which may be releasedthrough the lens body 120 including but not limited to timolol.

FIG. 5 shows a contour map of a lens due to inflation of the opticalchamber of the cavity by simulated action of lower eyelid on the contactlens. When the lower eyelid engages lower chamber 116, which comprises aliquid reservoir, fluid is passed to inner optical chamber 114, throughchannel 118, so as to increase the curvature of the inner opticalchamber 114 and provide optical power for near vision. The lens 100 maycomprise a polymer with a sufficient amount of cross-linking so as toretain fluid in the inner optical portion 114 when the lower portion 116engages the eyelid to generate additional plus power to correct nearvision of the eye upon down gazing at an object. Although the polymercan allow equilibrium, the amount of fluid released from the lens duringaccommodation is sufficiently low to allow optical correction.

The range of additional power generated may be from about 0.5 D to 6.0 Dwherein the down-gaze may be in the range of 10° to 40° and the objectbeing viewed may be at a distance within a range of about 15 cm to 200cm. The central region of the optical zone above the optical chambershows in increased height of 75 um relative to the rest of the lens,which is more than adequate to provide near vision to correct presbyopiawith optical power within the range from about 0.5 D to 6.0 D, forexample within a range from about 0.5 D to about 3 D.

The fluid 112 of the contact lens body 120 may comprise a refractiveindex within a range from about 1.31 to about 1.37 (also from about 1.33to about 1.36). The contact lens body 120 may comprise an index ofrefraction within a range from about 1.37 to about 1.48 (also from about1.37 to about 1.45). The refractive index of the contact lens materialcan be greater than the index of refraction of the fluid within thecavity, for example.

The cavity lens embodiments disclosed herein are well suited forcombination with many prior art lenses, including rotationallystabilized contact lenses.

FIG. 6 shows a stabilized contact lens suitable for combination with thecavity lens and insert as described herein. The stabilized lens isdescribed in the following patent applications: U.S. Ser. No.62/254,080, filed on 11 Nov. 2015, entitled “ROTATIONALLY STABILIZEDCONTACT LENS”; and U.S. Ser. No. 62/255,242, filed on 13 Nov. 2015,entitled “ROTATIONALLY STABILIZED CONTACT LENS” , the full disclosuresof which are incorporated herein by reference.

Lens 100 comprises an arrangement of structures to stabilize the lens.An upper stabilization zone 210 is generally located above the opticalzone 170. Upper stabilization zone 210 comprises a crescent shape. Alower stabilization zone 220 is located below the upper stabilizationzone and extends substantially around the optical zone 170. Lowerstabilization zone 220 comprises a generally annular shape and extendsaround at least about half of the optical zone 170. Lower stabilizationzone 220 comprises an upper boundary shaped to fit and correspond to thelower boundary of the upper stabilization zone. The lower stabilizationzone 220 comprises a thickness greater than the upper stabilization zonein order to stabilize the lens on the eye.

Lens 100 comprises a pressure sensitive zone 230 coupled to the opticalzone 170. Pressure sensitive zone 230 comprises a lenticular shape witha thickness less than the lower stabilization zone 220, in order tocouple pressure from the eyelid to a pressure sensitive structure withinthe pressure sensitive zone. Pressure sensitive zone 230 is generallylocated between the lower boundary of the lens and the optical zone 170.The lower stabilization zone 220 comprises a lower boundary shaped tofit and correspond to the upper boundary of the pressure sensitive zone230. Lens 100 comprises a midline 240 extending through a center 250 andcorresponding to a 90 degree axis of the lens 100. The stabilizingstructures of the lens can be symmetrically disposed about the midline240.

Optical zone 170 may comprise a pressure sensor or lower chamber fluidicmodule coupled to the pressure sensing zone 230 as described inapplication PCT/US2014/071988, the full disclosure of which isincorporated by reference herein.

Optical zone 170 may comprise an optical fluidic chamber configured toincrease curvature in response to eyelid pressure on the pressuresensing zone 230. The pressure sensing zone 230 comprises a fluidicreservoir chamber coupled to the optical chamber with a channelextending there-between to pass fluid to the optical chamber in responseto eyelid pressure.

In an alternative embodiment, optical zone 170 may comprise a liquidcrystal material between electrodes with the pressure sensing zone 230comprising a pressure sensor coupled to the electrodes with a circuit toincrease optical power of the liquid crystal material in response toeyelid pressure sensed with the pressure sensor.

The optical zone 170 comprises a maximum dimension across, such as adiameter 180 of the optical zone. The lens 100 comprises a maximumdimension across, such as diameter 190.

The upper stabilization zone 210 and lower stabilization zone 220 mayeach comprise a surface area greater than the pressure sensing zone inorder to stabilize the lens.

FIG. 7 shows a contact lens 100 comprising a sensor 150 wherein at leasta portion of the sensor is located within the cavity 110. Cavity 110 maybe formed over at least a portion of a sensor 150 embedded withincontact lens 100 in order to improve coupling of the sensor 150 to theexternal environment of the lens, for example tear fluid brought intocontact with the contact lens above the active sensor region 152.Movement of the lower eyelid 160 can provide fluid to the externalsurface of the contact lens near the sensor. Active sensor region 152may be exposed to the fluid within the cavity of the lens and thereforeable to better measure the tear fluid as said active sensor region 152is not in direct contact with the material of lens 100. The contact lensmay comprise the stabilized lens as described herein.

Sensor 150 may comprise one or more of a pressure sensor, a glucosesensor, a biomarker sensor, an electrical sensor, and a sensor havingion specific microelectrodes. The sensor 150 may comprise a volume of nomore than about 1.0 mm³, for example.

FIG. 8 shows a method of manufacturing a lens comprising a cavity formedby dissolving an insert, in accordance with embodiments. A base layer oflens material may be generated. A small amount of about 10 uL of lenspre-polymer may be placed in a lower mold cavity cup (STEP 1) andpartially cured (STEP 2) using UV light, or other appropriate curingmethod as defined by the pre-polymer in use. Next, an insert with athree-dimensional structure, such as insert 140 described herein, may beformed (STEP 3) and placed atop the partially cured resin layer residingin the lower mold cavity cup (STEP 4). Additional pre-polymer may thenbe delivered to the mold, which may comprise an insert and partiallycured resin, in such quantities that there is enough to complete lensformation (STEP 5). The lens may then be fully polymerized by curingunder UV light, for example at a wavelength of about 390 nm (STEP 6).The lens may then be removed from the mold (STEP 7), optionally placingthe lens and mold in saline and sonicating to facilitate de-molding(STEP 8), and hydrated for about 2-6 hours (STEP 9). Following initialhydration, the lens may be washed in dilute NaOH, for example 0.01 M(STEP 10), and further hydrated in saline for about 6-24 hours (STEP11). The saline may be replenished at least once during the hydration ofSTEP 11 (STEP 12). Upon hydration of the lens, the insert is dissolvedin order to form a cavity with the desired shape within the lens bodyand the dissolved insert material may diffuse out of the lens body (STEP13).

The method of FIG. 8 shows a method of manufacturing a cavity in a bodyof a material in accordance with an example. A person of ordinary skillin the art will recognize many variations. The steps can be performed inany order. Some of the steps can be added or removed. Materials used maybe altered such that steps may be changed. For example the pre-polymerused to for the lens body may be cross-linked through methods other thanphoto-polymerization, such as use of catalysts, therefore curing stepsmay be altered to include such methods.

Turning again to FIG. 5, the inner optical chamber 114 provides anincreased elevation contour to the upper surface of the lens in order toprovide optical power with fluid from the lower chamber 116. The upper(anterior) surface of the lens 100 has an approximately sphericalprofile over the optical portion of the lens corresponding to the inneroptical chamber 114. The surface elevation increases as shown from about0.006 mm from the outer portion of the optical zone to about 0.075 mm atthe center of the optical zone. A transition zone around the opticalzone may comprise an elevation within a range from about 0.000 mm toabout 0.006 mm, for example. The lower chamber 116 may also comprise anincreased surface elevation profile in relation to other locations ofthe lens 100. The lower chamber 116 may comprise an elevation within arange from about 0.006 mm to about 0.040 mm as compared to adjacentlocations of the lens 100, for example.

While the hydrogel of the contact lens body may comprise one or more ofmany hydrogel materials, in many embodiments the hydrogel compriseshydroxyethyl methacrylate (HEMA). The hydrogel comprising HEMA maycomprise channels or pores sized to allow water to diffuse into and outof the cavity from the exterior of the contact lens body as describedherein. The channels of the hydrogel contact lens body may be sized toallow a disinfectant to flow from the cavity chamber to the eye and toinhibit bacteria from entering the chamber from outside the lens body.The amount of cross-linking and cross-link density of the HEMA of thelens body can be configured to provide channels having appropriate sizesto allow water to diffuse in and out of the lens chamber and contain aportion of the solubilized material from the insert within the chamber.

The insert used to form the cavity may comprise one or more of manysolid materials as described herein. In many embodiments, the insertmaterial comprises polyvinyl alcohol (PVA), and the polymer chains ofPVA may comprise vinyl acetate (VAc) groups interspersed among the vinylalcohol groups. The co-polymer of PVA and PVAc 260 may be generated bypartially hydrolyzing polyvinyl acetate (PVAc) to PVA so as to have amixture of pendant groups along the polymer chain 262 comprising acetategroups 266 and alcohol groups 264 as shown in FIG. 9B. The insertmaterial may comprise a plurality of such co-polymer chains configuredto separate from each other when exposed to water so as to erode theinsert. The solid insert material may be composed of PVA and PVAc suchthat the PVAc is within a range from about 1% to about 20% by weight ofthe solid insert material and the PVA is within a range from about 99%to about 80% by weight of the solid insert material. Each of a pluralityof polymer chain of the insert material may comprise a number of vinylgroups having a number of pendent groups within a range from of about1000 to about 1500 pendant groups. For example, each of the plurality ofpolymer chains of the insert material may have about 1000 pendant groupswherein about 10% of the pendant groups comprise PVAc and about 90% ofthe pendant groups comprise PVA. Each of the plurality of PCA/Ac polymerchains of the insert material may comprise PVAc within a range fromabout 0.05% to about 10% and PVA within a range from about 90% to about99.5%. The PVAc pendant groups of each of the polymer chains of theinsert material may be randomly interspersed among the PVA pendantgroups. Each of the plurality of PVA/Ac chains of the insert materialmay have a molecular weight within a range from about 50 kilo Daltons(kD) to about 150 kD, for example. Each of the plurality of PVA/Acchains of the insert material may have a molecular weight within a rangefrom about 50 kD to about 100 kD, for example. Each of the plurality ofPVA/Ac chains of the insert material may have a molecular weight withina range from about 100 kD to about 110 kD, for example. The PVA/Acchains may comprise at least about 50% of the erodible insert material,and the amount of PVA/Ac chains within the material can be within arange from about 60% to 99%, for example.

The erodible insert material can be configured in many ways to providebeneficial properties to the material contained within the cavity. Theerodible insert material may comprise first polymer chains configured todissolve and travel through the body of the contact lens and secondpolymer chains configured to erode from the material and remain withinthe cavity. The amount of pendent acetate groups disposed along the PVAchains can be related to the solubility of the polymer chains. Forexample, the insert material may comprise first PVA polymer chainshaving less than about 10% vinyl acetate along the PVA chain, and secondpolymer chains having more than about 10% acetate along the PVA chains.The PVA chains having less than about 10% acetate can travel through thechannels of the contact lens body and the PVA chains having more thanabout 10% acetate can be inhibited from travelling through the contactlens body and remain within the cavity.

As shown in FIG. 9A, the cavity liquid 112 may comprise residualdissolved insert material 113 as described herein. The residual insertmaterial 113 may for example comprise polymer particles ornanoparticles. The residual dissolved insert material 113 may providethe cavity 110 with a refractive index gradient near the boundary of thecavity 110 to inhibit an abrupt change in the index of refraction andoptical artifacts that may be perceptible to a wearer. The refractiveindex gradient of the cavity 110 may comprise a greater index ofrefraction near the boundary of the cavity 110 and a lesser index ofrefraction away from the lens body 120. The refractive index gradientmay be formed by adsorption of the residual insert material 113 onto theexposed lens body material 120 defining the cavity 110 or by bondinginteractions between the lens body material 120 and the residual insertmaterial 113 for example. The residual insert material 113 may be moredensely packed at the boundaries of the cavity 110 than towards theinterior of the cavity 110 in order to generate a refractive indexgradient.

The refractive index gradient of the cavity may be formed by thecreation of one or more bonds, for example cross-linking or hydrogenbonding, between the insert material and the hydrogel lens material.Bonding may occur due to the addition of a cross-linking agent to theinsert for example. Alternatively or in combination, the insert materialmay be configured such that it comprises polymer chains with bothhydrophilic and hydrophobic pendant groups on them. The ratio ofhydrophilic to hydrophobic groups may determine the solubility of eachpolymer chain such that increasing amounts of hydrophobic pendant groupsdecreases the ability of the polymer chain to dissolve. The polymerchains with increased hydrophobic groups, e.g. acetate, may fold onthemselves to cover at least a portion of the acetate groups in order topartially dissolve within the cavity. Polymer chains which do not fullydissolve may form partially solubilized polymer particles that remain inthe chamber in the liquid contained within the cavity. The polymerparticles may be suspended in the cavity liquid. The particles may forma gel or gel-like network or substance within the cavity. Thesepartially solubilized polymer particles may comprise increased amountsof acetate groups as compared with more soluble polymer particles thatreadily dissolve and travel through the hydrogel contact lens body.These less soluble polymers may comprise insoluble side groups orhydrophobic pendant molecules (e.g. acetate) that inhibit diffusion ofthe less soluble polymer particles through the hydrophilic lens materialin order to provide a portion of the dissolved polymer particles withinthe chamber. The partially dissolved polymer particles can be adsorbedon an inner surface of the contact lens body defining the lens cavity.Exposed hydrophilic groups such as alcohols located on the partiallysolubilized polymer particles of insert material may be weakly bonded(e.g. with hydrogen bonds) with exposed hydrophilic side chains of thelens material at the cavity boundary.

Alternatively or in combination, the insert may be configured such thaterosion of the insert material generates particles of one or more sizes.Varying the size the particles in relation to the dimensions of thechannels of the lens body may alter the diffusion characteristics of theinsert material through the lens body. For example, particles withdimensions less than the dimensions of the channels may easily passthrough the channels and exit the lens. Particles with dimension greaterthan the dimensions of the channels may not pass through the channelsand may be contained within the cavity. In many embodiments, the insertmaterial erode into a plurality of particles with variable particlesizes such that a portion of the particles may exit the cavity throughthe channels and a portion of the particles may be contained within thecavity. For example, erosion of an insert material comprising a firstpolymer and a second polymer may lead to the formation of particles of afirst size and particles of a second size, respectively. The particlesof the first size may have dimensions less than the dimensions of thechannels and thus diffuse out of the cavity. The particles of the secondsize may be larger than the channels and thus remain within the cavity.The erodible insert material may for example comprise a first watersoluble polymer material and a second less soluble or insoluble polymermaterial. The first water soluble polymer material may have a molecularweight less than the second polymer material such that the secondpolymer material remains within the cavity formed by dissolution of thefirst soluble polymer material. The molecular weight of the firstpolymer may be such that dissolved particles of the first polymer areable to pass through channels in the lens body material and diffuse outof the lens. The molecular weight of the second polymer material may besuch that particles of the dissolved or partially dissolved secondpolymer are inhibited from passing through the channels. The particlesremaining in the cavity may form a refractive index gradient asdescribed herein.

The interface of the interior surface of the contact lens body can beconfigured in many ways to define the provided the graded index havingthe refractive index gradient extending between the contact lens bodyand the liquid contained within the cavity. The eroded material from theinsert within the chamber from the insert may comprise partiallysolubilized particles adsorbed to the surface of the contact lensmaterial on the interior surface defining the cavity. The adsorbedparticles may comprise polymer particles comprising acetate groups, forexample. Alternatively or in combination, the eroded material maycomprise water insoluble particles that remain after dissolution ofwater soluble material. The particles remaining within the chamber canbe adsorbed on the interior surface of the contact lens body definingthe cavity. The plurality of particles may comprise a maximum dimensionacross greater than about a quarter of a wavelength of visible light inorder to inhibit light scatter from the particles. For example, theplurality of particles may comprise a maximum dimension across of nomore than about 150 nm, and the maximum dimension across can be within arange from about 5 nm to about 150 nm. Alternatively or in combination,the maximum distance across can be within a range from about 10 nm toabout 100 nm, for example. The particles within these ranges canincrease the index of refraction with acceptable amounts of lightscatter that are not perceivable by the wearer.

Alternatively or in combination, the gradient refractive index can beprovided by polymer side chains extending from the lens body into thecavity. The lens material may for example comprise HEMA. Hydrophilicside groups or chains on the HEMA may prevent the hydrophobic acetateside chains of the solubilized polymer from diffusing out the cavity.Hydrophilic pendant groups on the polymer, for example PVA groups on aPVA-co-PVAc (PVA/Ac) polymer insert material, may hydrophilically bondwith the HEMA at the cavity-lens body interface to provide a refractiveindex gradient as described herein. The partially solubilized materialwithin the chamber from the insert when the lens is worn may comprise nomore than about 10% by weight of the material within the chamber, forexample.

The partially solubilized material within the cavity may comprise anamount sufficient to provide an osmolality of the cavity. The cavityliquid may comprise an osmolality within a range from about 200 milliosmols per liter (mOsmol/L) to about 290 mOsmol/L, for example within arange from about 250 mOsmol/L to about 290 mOsmol/L.

FIG. 10 shows a contact lens 100 with a single outer reservoir 116. Thecavity 110 may be similarly shaped as described herein so as to comprisean inner optical chamber 114, a channel 118, and a peripheral reservoir116. The cavity 110 may be formed by dissolving, eroding, degrading, orotherwise solubilizing an insert as described herein such that the shapeof the cavity 110 corresponds to the shape of the insert. The insert maycomprise an erodible material shaped to have front and back surfaceseach having curvature corresponding to one or more surface of thecontact lens 100. The cavity 110 may be formed between anterior andposterior surfaces of the lens body 120. The cavity 110 may be shaped toadd negative optical power to the contact lens when light is refractedin a far vision configuration. The anterior and posterior surfaces ofthe lens body 120 may each comprise a radius of curvature about thecavity 110 to provide far vision correction when combined with thenegative power of the cavity 110.

The insert may comprise a circular region which defines the inneroptical chamber 114 upon dissolving. The insert may comprise an outerregion which defines the peripheral reservoir 116. The insert maycomprise an extension between the circular region and the outer regionwhich defines the channel 118. The inner optical chamber 114 maycomprise a diameter 115 which corresponds to the diameter of a circularregion of the insert. The channel 118 may comprise a maximum dimensionacross 149 which corresponds to the maximum dimension across theextension of the insert. The maximum dimension across 149 of the channel118 may be less than the diameter 115 of the inner optical chamber 114,therefore the maximum dimension across of the extension may be less thanthe diameter of the circular region of the insert. The lower chamber 116may comprise a maximum dimension across 117 which corresponds to themaximum dimension across the outer region of the insert. The maximumdimension across 117 of the lower chamber 116 may be greater than themaximum dimension 149 of the channel 118, and the maximum dimensionacross of the outer region may be greater than the maximum dimension ofthe extension.

The insert may comprise an optically smooth surface such that the formedcavity 110 comprises optically smooth inner anterior and posteriorsurfaces so as to allow vision correction as described herein. Theerodible lens insert may comprise an RMS roughness of no more than about50 nm for example. The RMS roughness of the insert can be greater,depending on the difference between the difference between the index ofrefraction of the liquid contained in the cavity and the index ofrefraction of the lens body. The RMS roughness of the insert can bewithin a range from about 5 nm to about 1000 nm, for example within arange from about 10 nm to about 500 nm. The inner surface of the cavitymay be defined by an upper and a lower portion of the lens bodyextending across the optically used portion of the lens, and thesesurfaces may have RMS roughness similar to the insert. The inner surfaceof the cavity may have a surface roughness RMS value of about 50 nm orless in order to provide clarity and allow for vision correction, forexample.

The insert may have a tapered edge so as to reduce astigmatism, prism,or other aberrations that may be related to an abrupt change inrefractive index near the boundary of the cavity 110 formed in the lensmaterial 120.

Inflation of the optical chamber 114 of the cavity 110 may occur byaction of lower eyelid on the contact lens during down gaze as describedherein. When the lower eyelid engages the lower chamber 116 during downgaze, fluid is passed to inner optical chamber 114, through channel 118,so as to increase the curvature of the inner optical chamber 114 andprovide optical power for near vision. The curvature of the inneroptical chamber 114 may be reduced again upon returning to a primarygaze for far vision. FIG. 10 shows various locations which the lowereyelid may rest on the peripheral chamber 116 during down gaze (shown indashed lines) or primary gaze (shown in solid lines). The lower eyelidmay engage the peripheral chamber 116 during primary gaze to varyingdegrees. For example, during a minimum primary gaze 276 the lower eyelidmay not engage the peripheral chamber 116 at all. An average primarygaze 274 may result in the lower eyelid contacting a lower portion ofthe peripheral chamber 116. A maximum primary gaze 272 may result in thelower eyelid contacting about half of the peripheral chamber 116. Thetransition to down gaze may have similar variations, with a minimum downgaze 286 engaging a lower portion of the chamber 116, an average downgaze 284 engaging about half of the chamber 116, and a maximum down gaze282 engaging all or nearly all of chamber 116. The transition betweenprimary gaze and down gaze, and the corresponding change in lower eyelidposition, forces fluid from the peripheral reservoir 116 into the inneroptical chamber 114 where it may provide increased optical power fornear vision.

The cavity 110 may comprise a different index of refraction (alsoreferred to herein as a refractive index) than the hydrogel material ofthe lens body 120 surrounding the cavity 110 as described herein. Therefractive index of the cavity may be different by at least about 0.10from the refractive index of the material of the lens body 120. Therefractive index of the cavity may for example be different by at leastabout 0.05 from the refractive index of the material of the lens body120. The refractive index of the cavity may for example be different byat least about 0.03 from the refractive index of the material of thelens body 120. The difference in the refractive indices of the cavity110 and the lens body 120 may provide optical power to the inner opticalchamber 114.

The cavity 110 may comprise a similar index of refraction as thehydrogel material of the lens body 120. The refractive index of thecavity may be within about 0.10 of the refractive index of the lens bodymaterial 120. The refractive index of the cavity may for example bewithin about 0.05 of the refractive index of the lens body material 120.The refractive index of the cavity may for example be within about 0.03of the refractive index of the lens body material 120.

FIG. 11 shows a contact lens 100 with a progressive peripheral reservoir116. The cavity 110 may be formed as described herein. Similar to theembodiment shown in FIG. 10, the cavity 110 may comprise an inneroptical chamber or central reservoir 114, a peripheral reservoir orlower chamber 116, and a channel 118 extending there between. Thethickness 111 of the cavity 110 may be constant such that the thicknessof the inner optical chamber 114 and the thickness of the peripheralreservoir 116 are about the same when the peripheral reservoir 116 isnot engaged by the lower eyelid. The peripheral reservoir 116 mayfurther comprise a primary gaze portion 270 configured to be engaged bythe lower eyelid during far vision and a down gaze portion 280configured to be engaged by the lower eyelid during near vision.Compression of the primary gaze portion 270 may provide an intermediateamount of optical power change to the central reservoir 114 when the eyeis between a maximum primary gaze 272 (for example when staring straightahead into the distance) and a minimum primary gaze 276 (for examplewhen glancing at something low to the ground at a distance). As the gazecontinues down and moves nearer, more of the peripheral reservoir 116may be engaged, including the down gaze portion 280, so as to furtherincrease optical power in the inner optical portion 114. A measuredamount of fluid may be contained within the portions of the peripheralreservoir 116 so as to provide calculated responses of the lens 100 tothe needs of the wearer. In this way, the lens 100 may provide a rangeof optical powers suited to multiple eye positions similar to the wayprogressive lenses in glasses function.

FIG. 12 shows a contact lens 100 with two peripheral reservoirs 116 a,116 b. The cavity 110 may be formed as described herein. The cavity 110may comprise an inner optical chamber 114, a first outer chamber orperipheral reservoir 116 a, a second outer chamber or peripheralreservoir 116 b, and one or more channels 118 extending therebetween.The first outer chamber 116 a may be located inferior to the inneroptical chamber 114. The second outer chamber 116 b may be locatedinferior to the inner optical chamber 114. The first outer chamber 116 amay be located inferior to the second outer chamber 116 b. The first andsecond outer chambers 116 a, 116 b may each comprise an amount of fluidto provide near vision correction. Engagement of the first outer chamber116 a by the lower eyelid may provide a first about of fluid to theinner optical chamber 114 and provide intermediate vision correction. Asthe gaze is directed further down, the second outer chamber 116 b mayalso be engaged by the lower eyelid and the fluid of the second outerchamber 116 b may be combined with the fluid from the first outerchamber 116 a and provide near vision correction to the inner opticalchamber 114 of the lens 100. The amount of fluid in each outer chamber116 a, 116 b may be measured to as to have the desired amount ofintermediate and near vision correction. For example, the amount offluid in the first peripheral reservoir 116 a may be such that itprovides 1 D of increased optical power to the inner optical chamber 114when compressed for intermediate vision. The fluid in the secondperipheral reservoir 116 b may have enough fluid to provide anadditional 1 D of increased optical power, thus when both the firstouter chamber 116 a and second outer chamber 116 b are compressed theinner optical chamber 114 is provided 2 D of total increased opticalpower for far vision.

The cavity 110 of any of the embodiments described herein may comprise afluid in equilibrium with an outside liquid. For example, the cavityfluid may comprise one or more of water, saline, or tear fluid. Waterand other fluids may diffuse in and out of the contact lens body 120 tothe cavity 110 from an external surface of the contact lens body 120.The cavity 110 may be in equilibrium with the tear fluid of the eye whenplaced on the eye of a wearer. For example, the liquid contained withinthe cavity may be at least partially released by the hydrogel lens body120 onto the eye, for example to provide hydration. The liquid releasedby the cavity may be replaced with tear fluid. The cavity may forexample comprise a porous cavity.

The peripheral reservoir can be configured in many ways when connectedto the inner optical chamber in order to provide accommodation. In manyinstances, the upper lid may contribute to accommodation of the lens.The upper lid may engage the fluid-filled cavity during down-gaze orsquinting, thereby compressing the cavity and altering the shape of atleast the inner optical chamber in order to alter the optical power asdescribed herein. The peripheral chamber may be connected to the inneroptical chamber and sized and shaped in many ways, for example with anannular peripheral chamber extending around the inner optical chamber.Alternatively or in combination, the upper lid may engage an upperreservoir disposed above the inner optical chamber of the cavity. Theperipheral reservoir described herein may be an upper reservoir or alower reservoir as desired by one of ordinary skill in the art in orderto provide accommodation as described herein. The upper reservoir may becoupled to the inner optical chamber by an upper channel to allow fluidto flow between the upper reservoir and the inner optical chamber. Thecavity may comprise any combination of an inner optical chamber, anupper reservoir, and a lower reservoir. The cavity may for examplecomprise an inner optical chamber coupled to an upper reservoir by anupper channel and a lower reservoir by a channel as described herein.The cavity may alternatively comprise an inner optical chamber and anupper reservoir without a lower reservoir. Engagement of the upperreservoir with the upper eyelid may function to adjust the optical powerof the lens in a near vision configuration or far vision configurationin a manner substantially similar to that of the lower reservoirdescribed herein.

As described herein, the insert may be configured such that erosion ofthe insert material generates particles of one or more sizes. Theparticles may be sized such that they may easily pass through the one ormore channels of the lens body and exit the lens. The particles may havedimensions less than the dimensions of the channels. The one or morechannels may facilitate removal of the insert material. In someinstances, there may be no residual insert material left in the cavityfollowing erosion of the insert.

The lens material may be configured (e.g. with one or more channels asdescribed herein) such that particles or molecules (e.g. insert materialor therapeutic agents) with a radius of gyration within a pre-determinedrange may diffuse through the lens material (e.g. polymer) of the lensbody. The radius of gyration of a molecule able to diffuse through thepolymer may be within a range of about 0 nm to about 100 nm, for exampleno more than about 50 nm, or no more than about 15 nm. The radius ofgyration may be within a range defined between any two of the followingvalues: 0 nm, 5 nm, 10 nm, 15 nm, 20 nm, 25 nm, 30 nm, 40 nm, 50 nm, 60nm, 70 nm, 80 nm, 90 nm, and 100 nm.

The cavity may comprise a therapeutic agent. The therapeutic may bereleased by the cavity to the eye as described herein. The therapeuticagent may be selected from a group consisting of: anti-infectives,including, without limitation, antibiotics, antivirals, and antifungals;antiallergenic agents and mast cell stabilizers; steroidal andnon-steroidal anti-inflammatory agents; cyclooxygenase inhibitors,including, without limitation, Cox I and Cox II inhibitors; combinationsof anti-infective and anti-inflammatory agents; decongestants;anti-glaucoma agents, including, without limitation, adrenergics,β-adrenergic blocking agents, α-adrenergic agonists, parasypathomimeticagents, cholinesterase inhibitors, carbonic anhydrase inhibitors, andprostaglandins; combinations of anti-glaucoma agents; antioxidants;nutritional supplements; drugs for the treatment of cystoid macularedema including, without limitation, non-steroidal anti-inflammatoryagents; drugs for the treatment of ARMD, including, without limitation,angiogenesis inhibitors and nutritional supplements; drugs for thetreatment of herpetic infections and CMV ocular infections; drugs forthe treatment of proliferative vitreoretinopathy including, withoutlimitation, antimetabolites and fibrinolytics; wound modulating agents,including, without limitation, growth factors; antimetabolites;neuroprotective drugs, including, without limitation, eliprodil; andangiostatic steroids for the treatment of diseases or conditions ofposterior segment, including, without limitation, ARMD, CNV,retinopathies, retinitis, uveitis, macular edema, and glaucoma.

The therapeutic agent may comprise a molecular weight within a range ofabout 18 Daltons to about 10 kD. The therapeutic agent may comprise amolecular weight within a range defined between any of the two followingvalues: 10 Daltons, 20 Daltons, 50 Daltons, 100 Daltons, 200 Daltons,500 Daltons, 1 kD, 2 kD, 3 kD, 4 kD, 5 kD, 6 kD, 7 kD, 8 kD, 9 kD, and10 kD.

The cavity contact lens as described herein can be configured to providechanges in optical power of at least +2 Diopters (D), for example atleast +3 D, in response to low amounts of increases in pressure, inorder to allow the contact lens to change shape to correct presbyopia inresponse to eyelid contact. The amount of internal pressure to increasethe optical power by at least +2 D, can be within a range from about 10Pascals (Pa) to about 100 Pa, for example within a range from about 20Pa to about 50 Pa. The thickness of the anterior and posterior lensportions defining the cavity can be sized as described herein toincrease or decrease the amount of deflection in the lens in response tointernal pressure generated by the eyelid. The modulus of the contactlens material can be increased or decreased to change the amount ofpressure increase to provide the correction. The modulus of the hydrogelcontact lens material as described herein and can be within a range fromabout 0.2 MPa to about 4 MPa, for example within a range from about 0.25MPa to about 2 MPa. In many instances, the modulus is related to theequilibrium water content, and the modulus can be decreased withincreasing amounts of hydration as described herein. The equilibriumwater content can be within a range from about 25% to about 80%, forexample within a range from about 30% to about 70% and within a rangefrom about 40% to about 65%. The volume of cavity can be within a rangefrom about 0.25 mm³ to about 10 mm³, for example within a range fromabout 0.5 mm³ to about 5 mm³.The internal pressure of the cavity can bemeasured by inserting a needle into the cavity and measuring thepressure with a manometer, for example, and other methods of measuringpressure known to one of ordinary skill in the art.

TABLE 1 lists examples of hydrogel materials, equilibrium water content,and moduli. Equilibrium Oxygen Water Content Permeability Material (%)Modulus (MPa) (Dk × 10−11) Lotrafilcon A 24 1.5 140 Lotrafilcon B 36 1.0110 Balafilcon A 33 1.1 99 Comfilcon A 48 0.8 128 Senofilcon A 38 0.72103 pHEMA 38 0.50 7.5 Omafilcon A 62 0.49 34 Galyfilcon A 47 0.43 60Etafilcon A 58 0.3 21

Although Table 1 is provided as an example, other materials as describedherein can be configured to have moduli and amounts of hydration asdescribed herein.

FIGS. 13A-13C show a contact lens comprising an internal cavity 110formed by erosion of an insert as described herein. The cavity 110 maybe formed by dissolving, eroding, degrading, or otherwise solubilizingan insert as described herein such that the shape of the cavity 110corresponds to the shape of the insert. The cavity 110 may be formedbetween anterior and posterior surfaces of the lens body 120. The insertmay comprise an erodible material as described herein. As the inserterodes, low molecular weight or highly soluble components of the insertmay readily diffuse through the lens body 120 while high molecularweight or insoluble components of the insert may have reduced diffusionas described herein. For example, the insert may dissolve into particlesof differing sizes, with higher molecular weight particles being unableto pass through the pores or channels in the lens body 120 while lowermolecular weight particles readily diffuse out of the cavity 110. Thecavity 110 may not comprise residual insert material as describedherein. The cavity 110 may comprise residual insert material asdescribed herein. Retention of residual insert material within thecavity 110 may change the osmotic pressure of the cavity 110 and causethe cavity 110 to swell as described herein. The amount of swelling orbulging of the cavity 110 may be controlled to achieve desired opticaland/or physical properties of the lens 100. The amount of swelling orbulging of the cavity 110 may be controlled by altering one or more ofthe temperature, the salinity of the surrounding solvent, the amount ortype of sugars in the insert or solvent, the molecular size of thedissolved insert materials, the rate of dissolution of the insertmaterials and their water uptake rate, the solvent and conditions ofinsert dissolution, or any combination thereof. For example, theswelling may be mitigated by increasing the heat of the solvent orincreasing the salinity of the solvent. Alternatively or in combination,the channel size of the lens body material may be increased to permitdiffusion of larger or less soluble particles through the lens andthereby alter the amount of residual insert material in the cavity 110and relieve the osmotic pressure of the cavity 110. The channel size maybe altered as described herein, for example by modifying the chemistryof the lens body formation. One or more channels or holes may bemechanically created in the lens body, for example with a syringe,needle, laser, or other method suitable for creating a hole.Alternatively or in combination, one or more holes may be made byshaping the insert such that it leaves behind a hole in the lens bodywhen eroded.

FIG. 13A shows a cross-sectional view of a contact lens 100 comprisingan internal cavity 110 and hole 310. Any of the contact lenses describedherein may further comprise one or more hole or channel 310. The hole orchannel 310 may comprise an opening in the lens body 120 which extendsfrom the cavity 110 to the external environment of the lens 100. One ormore holes 310 may be created by physically puncturing the lens body120. Alternatively or in combination, one or more holes 310 may becreated through chemical erosion of the lens body 120 or by altering thechemical properties of the lens body 120 prior to UV curing.Alternatively or in combination, one or more holes 310 may be generatedby a correspondingly-shaped protrusion on the insert. Hole 310 may besized to facilitate the release of high molecular weight substances fromthe cavity, for example to control, reduce, or prevent bulging of thelens 100 as the cavity 110 is formed following dissolution or erosion ofan insert as described herein. The hole 310 may be positioned outside ofthe optical zone 170 to prevent visual aberrations. The hole 310 may beposition inside the optical zone 170.

FIG. 13B shows a cross-sectional view of an insert 140 comprising aprotrusion 312. The channel 310 may for example be formed during thecuring process of the lens 100. The insert 140 may be configured so asto form a corresponding hole in the lens upon erosion of the insert 140to form the cavity. The insert 140 may be shaped substantially similarto any of the inserts described herein such that a cavity is formedwithin the lens body when the insert material erodes and diffuses out ofthe lens. The insert 140 may comprise a protrusion 312 which extendsbeyond the upper surface 142 or lower surface 144 of the insert 140towards an external surface of the lens. The protrusion 312 may beshaped such that it extends up to or beyond the surface of the lensafter the lens is formed around the insert as described herein. Theprotrusion 312 may be located anywhere on the insert 140. The protrusion312 may for example be on an outer edge of the insert as shown in FIG.13B. The protrusion 312 may be disposed on an internal surface 142, 144of the insert away from the edge. The protrusion 312 may protrudetowards the posterior surface of the lens, the anterior surface of thelens, or both. It will be understood that the protrusion 312 may belocated on any part of the insert 140 in order to form a hole in thelens body extending into the cavity upon erosion of the insert material(as shown in FIG. 13A).

FIG. 13C shows a cross-sectional view of a contact lens 100 comprisingan internal cavity 140 and filled-in hole 314. After the lens hashydrated and the insert has eroded, the hole may be filled in 314 inorder to create a final lens 100 comprising an internal cavity 110substantially similar to any of the lenses described herein. The holemay be filled in 314 with any suitable material, for example the same ordifferent material used to form the lens, and then bonded or hardened tocomplete the lens body 120. For example, the filled-in hole 314 maycomprise lens body material which was injected into the hole with asyringe and UV-cured to seal the hole. The hole may be filled in,plugged, sealed, sealed with polymer comprising a polymer of the contactlens, welded, or otherwise closed using techniques known to one ofordinary skill in the art following erosion of the insert and formationof the cavity.

The insert described herein can be sized and shaped in many ways. Theinsert may comprise a three dimensional shape profile. The threedimensional shape profile may comprise an outer boundary defining theouter boundary of the cavity 110. The shape profile may comprise one ormore curved surfaces corresponding to one or more surfaces of thecontact lens, for example corresponding to the lower base curvature ofthe contact lens. The insert may be fabricated via casting, extrusion,molding, lamination, laser etching or ablation, or any other techniqueknown to those skilled in the art. The insert may be formed by anycombination of techniques to produce a desired three-dimensionalprofile.

The lens may be formed around the insert as described herein. A baselayer of lens material may be generated by the addition of a smallamount of lens pre-polymer to a lower mold cavity cup. The pre-polymermaterial may be partially cured using UV light or other curing methods.The partially cured resin layer (e.g. base layer or first portion) maybe viscous or solid. The insert may be formed and/or placed atop thepartially cured resin layer residing in the lower mold cavity cup. Theinsert may be partially inserted into or submerged in the partiallycured base layer residing in the lower mold cavity cup to secure theinsert. The insert may be placed on the base layer by a robotic arm.Additional pre-polymer may then be delivered to the mold, which maycomprise an insert and partially cured resin, in such quantities thatthere is enough to generate a top layer of lens material (e.g. to form asecond portion) and complete lens formation. The robotic arm may deliversome or all of the additional pre-polymer before, during, or afterplacement of the insert on the base layer. The lens may then be fullypolymerized by curing under UV light for example. The lens may then behydrated and the insert dissolved in order to form a cavity with thedesired shape within the lens body and the dissolved insert material maydiffuse out of the lens body as described herein. Alternatively or incombination, the insert may be formed on an intermediate layer ofmaterial, for example lens material or any other material as desired.The intermediate layer may be placed atop the uncured or partially curedbase layer of lens material prior to addition of the top layer lensmaterial and completion of lens formation.

After hydration and erosion of insert to form the cavity, the contactlens body may comprise a first portion on a first side of the cavitycorresponding to the base layer of polymer poured as described herein.The contact lens body may further comprise a second portion on a secondside of the cavity corresponding to the top layer of polymer poured asdescribed herein. The cavity may extend between the top layer and thebottom layer. Internal surfaces of the top layer and the bottom layer,shaped by the erosion of insert, may define the cavity. The top layerand bottom layer may be bonded together away from the cavity (e.g. wherethe insert was not) as described herein. The cavity may comprise a fluidas described herein. The cross-linked polymer of the lens body exposedat the cavity edge may directly contact the fluid within the cavity. Theinterface at which the top layer and the bottom layer are bondedtogether may be undetectable. The interface at which the top layer andthe bottom layer are bonded together may be detectable, for example bydark field microscopy as known to one of ordinary skill in the art. Forexample, the lens may be bisected along a midline and dark fieldmicroscopy may be used to visualize the interface between the two curedregions or layers via light scattering.

The insert may be positioned during formation of the lens such that thecavity, or a portion of the cavity, for example the inner opticalchamber, is eccentric with the contact lens. The insert may bepositioned during formation of the lens such that the cavity isconcentric within the lens. The insert may be positioned and/or thecavity may be formed such that the cavity is concentric with the pupilwhen the lens is placed on the eye. The inner optical chamber can bepositioned in many ways in relation to the contact lens in order toaccommodate anatomical variability of the eye. For example, the inneroptical chamber may be positioned within the soft contact lens away froma center of the contact lens such that the inner optical chamber isconcentric with the pupil. Alternatively, the inner optical chamber canbe concentric with the contact lens. A person of ordinary skill in theart will recognize that the pupil may be located away from the center ofthe cornea and design the contact lens accordingly in accordance withthe embodiments disclosed herein. This approach allows the center of theinner optical chamber to be centered on the pupil when the soft contactlens is placed on the eye. The inner optical chamber may be concentricor eccentric within the soft contact lens, such as with respect to thecenter of the soft contact lens. The lens may be configured such thatthe optical zone is concentric or eccentric with respect to the centerof the lens. The lens may be configured such that the optical zone isconcentric or eccentric with respect to the pupil.

The diameter or maximum dimension across of the optical zone and/orinner optical chamber may be sized to match the pupil based onphysiological norms. The diameter of the optical zone or inner opticalchamber may be within a range of about 2.5 mm to about 6 mm, for examplewithin a range of about 3 mm to about 6 mm.

Erosion or dissolution of the insert may result in the formation of acavity comprising an optically smooth surface of an inner portion of thecavity through which light passes to correct vision. The opticallysmooth surface may comprise no visually perceptible artifacts (e.g. lessthan about 0.1 D) when worn by a patient. The optically smooth surfacemay have a wavefront distortion of about 0.3 microns or less measuredthrough the optically smooth surface, for example within a range definedbetween any two of the following values: about 0 microns, about 0.01microns, about 0.025 microns, about 0.05 microns, about 0.075 microns,about 0.1 microns, about 0.125 microns, about 0.15 microns, about 0.175microns, about 0.2 microns, about 0.225 microns, about 0.25 microns,about 0.275 microns, and about 0.3 microns. The optically smooth surfacemay have an RMS value of about 0.2 microns of less, for example within arange defined between any two of the following values: about 0 microns,about 0.01 microns, about 0.025 microns, about 0.05 microns, about 0.075microns, about 0.1 microns, about 0.125 microns, about 0.15 microns,about 0.175 microns, and about 0.2 microns. Erosion of the insertmaterial may result in the formation of a cavity comprising residualsurface structure corresponding to the surface structure of the insert.The residual surface structure may comprise a three-dimension patternleft behind due to three-dimensional patterning on the surface of theinsert. Alternatively or in combination, the residual surface structuremay comprise residual insert material. The inner surface of the cavitymay have an RMS value within a range defined between any two of thefollowing values: about 5 nm, about 10 nm, about 15 nm, about 25 nm,about 50 nm, about 100 nm, about 200 nm, about 300 nm, about 400 nm,about 500 nm, about 600 nm, about 700 nm, about 800 nm, about 900 nm,and about 1000 nm. The inner surface of the cavity may have an RMS valueof about 50 nm or less.

The shape-changing portion of the lens (e.g. the inner optical chamberand/or peripheral reservoir(s) as described herein) used to correctvision may have RMS optical path difference aberrations of about 0.4microns or less in a far vision configuration when placed on the eye.The RMS optical path difference values may be measured on-eye withHartmann-Shack wavefront aberrometry or other techniques as are known toone of ordinary skill in the art. The shape-changing portion of the lens(e.g. the inner optical chamber and/or peripheral reservoir(s) asdescribed herein) used to correct vision may have RMS optical pathdifference aberrations of about 0.4 microns or less in a near visionconfiguration when placed on the eye. The RMS optical path differenceaberrations may for example within a range defined between any two ofthe following values: about 0 microns, about 0.01 microns, about 0.025microns, about 0.05 microns, about 0.075 microns, about 0.1 microns,about 0.125 microns, about 0.15 microns, about 0.175 microns, about 0.2microns, about 0.225 microns, about 0.25 microns, about 0.275 microns,about 0.3 microns, about 0.325 microns, about 0.35 microns, about 0.375microns, and about 0.4 microns.

The insert may comprise any of the insert materials described herein.The insert 140 may have a thickness within a range from about 0.5microns to about 100 microns. The insert 140 may have a thickness withina range bounded by any two numbers from Table 2, for example within arange of about 0.5 microns to about 10 microns or within a range ofabout 4 microns to about 60 microns. The insert may have a thicknessgreater than about 100 microns. The insert may have a thickness within arange defined between any two of the following values: about 0.5microns, about 15 microns, about 75 microns, about 100 microns, about150 microns, and about 200 microns.

Table 2 shows the range of values that the insert thickness can take.

TABLE Insert thickness values. Insert thickness (microns) 0.5 1 2 4 5 1020 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200

The insert may comprise a material capable of deforming without breakingat room temperature. The insert may comprise a material capable of beingbent to a radius of curvature within a range from about 5 mm to about 1m, for example within a range defined between any two of the followingvalues: about 5 mm, about 10 mm, about 25 mm, about 50 mm, about 100 mm,about 200 mm, about 300 mm, about 400 mm, about 500 mm, about 600 mm,about 700 mm, about 800 mm, about 900 mm, and about 1000 mm. The insertmay optionally comprise an elastic material. The insert may comprise aflexible, non-brittle material.

Factors affecting the dissolution of the insert may include themolecular size of the dissolved insert materials, the rate ofdissolution of the insert materials and their water uptake rate, thesolvent and conditions of insert dissolution, or any combinationthereof. The insert may be dissolved, eroded, degraded, or solubilizedwith or without forming a bulge in the lens cavity.

The insert may be formed of any material suitably dissolvable, erodible,degradable, or solubilizable by an aqueous solution, an alcohol, orother solvent, or any combination thereof. The insert material maycomprise one or more low molecular weight components capable ofdiffusing through the lens body material upon hydration, exposure to anaqueous solution, exposure to an alcohol-based solution, exposure to anorganic solvent, or any combination thereof. The insert material maycomprise one or more components with a reduced capacity for diffusionthrough the lens body as described herein. The insert material may bephoto-curable. The insert material may be moldable. The insert materialmay be extrudable. The insert material may comprise a sugar such asfructose, galactose, glucose, glyceraldehyde, lactose, maltose, ribose,sucrose, or any other monosaccharides, disaccharides, or polysaccharidessuch as cellulose or methylcellulose. The insert material may comprise asugar alcohol such as arabitol, sorbitol, D-sorbitol, erythritol,fucitol, galactiol, glycerol, iditol, inositol, isomalt, lactitol,maltotetraitol, maltitol, maltotritol, mannitol, inositol, myo-inositol,polyglycitol, ribitol, sorbitol, threitol, xylitol, or any other sugaralcohol. A sugar-based insert material may comprise a low molecularweight and may thereby be beneficial when a reduction in bulging isdesired as described herein. The insert material may comprise a saltsuch as sodium chloride, sodium carbonate, potassium chloride, or anyother salt. The insert material may comprise dimethyl sulfoxide (DMSO),N-vinylpyrrolidone (NVP), polyethylene glycol (PEG), poly sodiummethacrylate, METHOCEL™ E6, or any of the materials described herein.The insert material may comprise polyvinyl alcohol (PVA), and thepolymer chains of PVA may comprise vinyl acetate (VAc) groupsinterspersed among the vinyl alcohol groups as described herein. Theco-polymer of PVA and PVAc may be generated by partially hydrolyzingpolyvinyl acetate (PVAc) to PVA so as to have a mixture of pendantgroups along the polymer chain comprising acetate groups and alcoholgroups. The insert material may be chosen to reduce deformation of thelens before, during, or after removal of the insert. The insert materialmay be any combination of the materials described herein.

The insert material may comprise one or more low molecular weightcomponents. The insert material may comprise a molecular weight within arange of about 1 g/mol (grams per mole) to about 50,000 g/mol, or withina range between any two weights therebetween. The insert material mayfor example comprise a molecular weight within a range of about 50 g/molto about 10,000 g/mol, for example within a range of about 50 g/mol toabout 5,000 g/mol, or within a range of about 50 g/mol to about 1000g/mol. For example, the insert material may comprise sodium chloridewhich as a molecular weight of 58.44 g/mol. The insert material maycomprise glucose which has a molecular weight of 180 g/mol. The insertmaterial may comprise isomalt which has a molecular weight of 334 g/mol.The insert material may comprise sucrose which has a molecular weight of342 g/mol.

The insert material may comprise a molecular weight within a range ofabout 50 g/mol to about 100,000 g/mol, or within a range bounded by anytwo numbers therebetween. The insert material may comprise a molecularweight within a range defined between any of the two following values:50 g/mol, 100 g/mol, 500 g/mol, 1,000 g/mol, 5,000 g/mol, 10,000 g/mol,25,000 g/mol, 50,000 g/mol, and 100,000 g/mol.

The insert material may comprise PVA or PVA/Ac as described herein. Themolecular weight of the PVA or PVA/Ac may be within a range of about 50Daltons (e.g. g/mol) to about 100,000 Daltons, or within a range boundedby any two numbers therebetween. The insert material may comprise PVA orPCA/Ac with a molecular weight within a range defined between any of thetwo following values: 50 Daltons, 100 Daltons, 500 Daltons, 1,000Daltons, 5,000 Daltons, 10,000 Daltons, 25,000 Daltons, 50,000 Daltons,and 100,000 Daltons. The insert material may comprise PVA or PVA/Ac witha molecular weight of less than about 13,000 Daltons.

The erodible inserts as described herein can be configured in many waysand may comprise sufficient strength to facilitate handling of theinsert in a free standing configuration, for example when the insert isplaced on a partially cured contact lens material. The insert maycomprise a combination of materials and thickness as disclosed herein inorder to allow the insert to be bent from a substantially planarconfiguration to a radius of curvature within a range from about 5 mm toabout 1 m. The insert may be resilient and capable of substantiallyreturning to an initial profile to being bent, for example returning atleast about 90% toward the initial profile from the deflected profile.The insert may comprise an additive as described herein to promoteflexibility. Although the insert can be optically smooth to an RMSroughness of approximately 50 nm or less, for example, the insert maycomprise greater amounts of roughness without affecting optical qualityof the lens, for example when the fluid of the optical cavity has anindex of refraction within about 0.1 of the fully hydrated contact lensmaterial defining the cavity. Although the roughness and surfacestructure of the insert may be imparted on the contact lens materialdefining the cavity subsequent to erosion of the insert, this magnitudeof such structure and roughness can be controlled by manufacturing theinsert such that the surface structure of the insert material impartedon the lens cavity does not provide user perceptible optical artifactsor degrade vision in many instances.

The lens 100 can be formed in many ways. The lens may also be fabricatedvia casting, extrusion, molding, lamination, or any other techniqueknown to those skilled in the art. The lens 100 may by formed bymolding, or the like. The lens 100 may be formed to any shape or size asdesired. The material of the lens may for example be a polymer thatforms a hydrogel in water or aqueous solution. The material of the lensmay comprise acofilcon A, acofilcon B, alfafilcon A, altraficon A,atlafilcon A, balafilcon A, bufilcon A, comfilcon A, crofilcon,deltafilcon A, dimefilcon A, droxifilcon A, efrofilcon A, enfilcon,epsifilcon A, etafilcon A, focofilcon A, galyfilcon A, heflicon A,heflicon B, hefilcon C, hilafilcon A, hilafilcon B, hioxifilcon A,hioxifilcon B, hioxifilcon D, isofilcon , lidofilcon A, lidofilcon B,lotrafilcon A, lotrafilcon B, mafilcon, methafilcon A, methafilcon B,narafilcon B, nelfilcon A, nescofilcon A, netrafilcon A, ocufilcon A,ocufilcon B, ocufilcon C, ocufilcon D, ocufilcon E, ocufilcon F, ofilconA, omafilcon A, phemfilcon, phemfilcon A, polymacon, perfilcon A,samfilcon A, scafilcon A, senofilcon A, sifilcon A, surfilcon A,teflicon, tetrafilcon A, tetrafilcon B, vasurfilcon A, vilfilcon A,xylofilcon A, or any combination thereof. One or more lens materials maybe used to form the lens. For example, the base layer may comprise adifferent lens material than the top layer.

Some or all of the lens material may be partially or fully cured before,during, or after the manufacturing process.

The insert material may be extracted from the lens body by exposure toan aqueous solution, an alcohol-based solution, an organic solvent, orany combination thereof. The insert material may for example beextracted from the lens body by saline. The insert material may beextracted from the lens body by an organic solvent such as an alcohol(e.g. ethanol), an ether (for example a cyclic either such astetrahydrofuran). The solvent may be miscible in water or an aqueoussolution. The insert material may be extracted from the lens body bysaline in combination with an organic solvent, for example an organicsolvent which is miscible with water such as isopropanol, methanol,tetrahydrofuran, or ethanol. The insert material may be extracted fromthe lens body at a temperature at or above room temperature. Forexample, the insert material may be extracted at a temperature within arange of about 20° C. to about 80° C. or any within a range of any twotemperatures therebetween. The insert material may be extracted at atemperature within a range of about 25° C. to about 60° C. The insertmaterial may be extracted at any temperature desired to achieveformation of the cavity. The insert material may be extracted from thelens body by any solvent or solution known to one of ordinary skill inthe art which is compatible with the lens material. Removal of theinsert material from the lens body to form the cavity may be aided bycirculation of the extraction solution or solvent about the lens body.

FIG. 14 shows a contact lens 100 comprising an internal cavity 110. Thecavity 110 may be substantially similar to any of the cavities describedherein. For example, the cavity 110 may comprise an inner opticalchamber 114 and one or more lower chambers (not shown) as describedherein. The inner optical chamber 114 may deflect in response tocompression of the one or more lower chambers as described herein.Deflection of the inner optical chamber 114 may provide opticalcorrection as described herein. Deflection of the inner optical chamber114 may provide increased optical power to provide near visioncorrection as described herein. The lens anterior side 104 may deflectwith the deflection of the inner optical chamber 114. Deflection of thelens anterior side 104 may provide optical correction, for exampleincreased optical power when the lens anterior side 104 is deflectedanteriorly by compression of the one or more lower chambers. The lensanterior side 104 may be deflected so as to provide uniform opticalcorrection, for example spherically. The lens anterior side 104 may bedeflected to as to provide non-uniform optical correction, for examplenon-spherically. The lens anterior side 104 may have a multifocalprofile 320 with regions of differing optical power. As an example,there may be a first region 322 with a high optical power, for example 3D, a second region 324 with a medium optical power, for example 2 D, anda third region 326 with a low optical power, for example 1 D. Thesenumbers are meant only as an example and those skilled in the art willrecognize that the lens 100 may be configured to accommodate manypossible values for optical power as desired. The multifocal profile 320can be made of distinct regions or may be continuous. The multifocalprofile 320 may have distinct regions of differing optical power. Themultifocal profile 320 may have a continuously varying region of opticalpower. The lens 100 may comprise a multifocal profile 320 in a nearvision configuration. Alternatively or in combination, the lens 100 maycomprise a multifocal profile 320 in a far vision configuration.

FIG. 15 shows a cross-sectional view of a hydrogel contact lens 100comprising an internal cavity 110. The cavity 110 may comprise residualinsert material as described herein. The residual insert material may becross-linked within the cavity 110, for example during UV-curing of thelens body around the insert prior to hydration. The residual insertmaterial may be cross-linked within the cavity 110 by a chemicalcross-linker prior to, during, or after hydration. The cross-linkedmaterial 268 may be free-floating or cross-linked to the exposed lenspolymer material at one or more locations. For example, the cross-linkedmaterial 268 may extend across the cavity 110 from the anterior edge 133of the cavity 110 to the posterior edge or base 132 of the cavity 110.Cross-linked material 268 may extend into the cavity 110 from one pointalong the anterior edge 133 to another point along the anterior edge133. Cross-linked material 268 may extend into the cavity 110 from onepoint along the posterior edge 132 to another point along the posterioredge 132. The cross-linked material 268 may form a network ofcross-linked polymer chains within the cavity 110 connected to theanterior edge 133, the posterior edge 132, any other surface definingthe cavity 110, or any combination thereof, or it may be unconnected tothe lens body surfaces defining the cavity 110. The insert material maycomprise any material which cross-links when exposed to UV light forexample. The insert material may comprise a UV blocking or absorbingmaterial in order to modify the extent or location of cross-linking. Theinsert may for example be coated in or comprise a UV blocking agent. Theinsert material may be selected so as to create desired arrangements ofcross-linking for optical, structural, or functional purposes.

In some embodiments, it may be desirable to prevent cross-linking of theresidual insert material. The insert material may comprise any materialwhich does not cross-link when exposed to UV light for example.Alternatively or in combination, the insert 140 may be coated in, mixedwith, made from, or otherwise created using a UV blocking or absorbingmaterial in order to prevent cross-linking of the insert material duringphoto-curing of the lens body 120.

FIG. 16 shows a contact lens 100 with a cavity 110 configured fortherapeutic agent delivery to the eye of the wearer. The cavity 110 maycomprise a therapeutic agent 330. The therapeutic agent 330 may compriseany of the drugs or therapeutic agents described herein. The therapeuticagent 330 may comprise a plurality of therapeutic agents, for example amixture or any number of therapeutic agents as desired. The therapeuticagent 330 may be introduced into the cavity 110 in any number of ways.For example, the insert which erodes to form the cavity may comprise thetherapeutic agent 330. Alternatively or in combination, the therapeuticagent 330 may be a coating on the insert. The therapeutic agent 330 mayremain in the cavity following dissolution of the insert. Alternativelyor in combination, the therapeutic agent 330 may be introduced into thecavity 110 following erosion of the insert or via the external solutionin which the lens 100 is stored. The external solution may be an aqueoussolution 204 containing the therapeutic agent 330 such that as theinternal cavity 110 comes to equilibrium with the external storagesolution, the therapeutic agent 330 diffuses across the lens body 120into the cavity 110. The storage solution may be of such aconcentration, temperature, composition, or any comparable parameter orcombination of parameters that the rate of diffusion can be controlledto load the cavity 110 with the desired amount of therapeutic agent 330.The therapeutic agent 330 may also be introduced into the cavity 110through any technique known to those skilled in the art.

The therapeutic agent 330 may be delivered to the eye when the lens 100is being worn via diffusion. The therapeutic agent 330 may diffuseacross a posterior side 106 of lens 100 to the eye, or across ananterior side of the lens. The posterior side 106 of the lens 100 mayact as a rate control structure. For example, the posterior side 106 ofthe lens 100 may comprise a thickness 107. The thickness 107 may besized in order to control the diffusion rate 332 of the therapeuticagent 330 through the posterior side 106 of the lens 100 onto thesurface of the eye. Alternatively or in combination, the pore size ofthe lens body 120 may be configured so as to control the rate ofdiffusion 332 of the therapeutic agent 330 through the posterior side106 of the lens 100. The molecular weight and/or size of the therapeuticagent may affect the rate of diffusion across the posterior side 105.The molecular weight of the therapeutic agent 330 may for example bewithin a range of about 18 to about 10 kilo Daltons. In manyembodiments, the molecular weight of the therapeutic agent is no morethan the molecular weight of the insert material, in order to allow thetherapeutic agent to diffuse out of the cavity and onto the eye whenworn. The therapeutic agent may comprise water to hydrate the eye, andother materials to retain water such as surfactants, for example.Although reference is made to the posterior side of the lens providing arate control structure, the anterior side of the lens may be similarlyconfigured.

Any range of molecular weights may be combined with any range or sizes,any range of thicknesses, or any combination thereof in order to achievea desired rate of diffusion of the therapeutic agent 330 out of thecavity 110, through the lens posterior side 106, and onto the eye. Forexample, for a given molecular weight of the therapeutic agent 330, thethickness 107 may be modified to achieve a desired therapeutic agentrelease rate.

Therapeutic amounts of the therapeutic agent 330 may cause a change inthe refractive index of the cavity. The change in the index ofrefraction may be within a range of about 0.01 to about 0.02 such thatvision is not significantly altered by the presence of the therapeuticagent 330. Alternatively or in combination, there may be a second cavityformed by a second insert outside the optical zone. The second cavitymay comprise the therapeutic agent 330 such that the therapeutic agent330 remains out of the optical zone of the lens. Such an approach couldbe a useful way to maintain the therapeutic agent delivery capabilitiesof the lens without affecting vision, especially for those sorts oftherapeutic agents which may be used in high concentrations or which mayaffect the index of refraction so as to reduce vision beyond a tolerablelevel. The cavity in the optical zone, the second cavity outside theoptical zone, or both cavities may comprise one or more therapeuticagent 330. The cavities may comprise different therapeutic agents 330 orthe same therapeutic agent 300. The cavities may comprise the sameconcentration of therapeutic agent 330 or different concentrations oftherapeutic agent 330. It will be understood that the lens 100 maycomprise any number of cavities of any size as desired to deliver anynumber or concentration of therapeutic agents as desired to any locationon the eye as desired. The cavity may be positioned so as to delivertherapeutic agent directly to the site of injury or infection forexample. One or more cavities may be positioned so as to generate atherapeutic agent concentration gradient across the surface of the eye.

The therapeutic agent 330 may comprise a half-life of about 1 day toabout 7 days to allow for the introduction of therapeutic agent 330 intothe cavity 110 from the external storage solution and/or to achievedesired release of the active compound or therapeutic agent 330 onto theeye. Alternatively or in combination, the therapeutic agent may comprisea solid to provide a substantially constant rate of release while thesolid remains present on the lens.

FIG. 17 shows a contact lens 100 with a cavity 110 near the posteriorlens surface 136 configured for therapeutic agent delivery to the eye ofthe wearer. Placement of the cavity 110 near the posterior lens surface136 may be useful to achieve the desired diffusion behavior. Placementof the cavity 110 near the posterior lens surface 136 may be useful toachieve the desired refractive behavior and may be situated in such away to be outside of the optical zone. The cavity 110 may be continuouswith one or more other cavities in the lens configured to deliverytherapeutic agents, aid in vision, or any other purpose disclosedherein. The cavity 110 may comprise a therapeutic agent 330. Thetherapeutic agent 330 may comprise any of the drugs or therapeuticagents described herein. The therapeutic agent 330 may comprise aplurality of drugs, for example a mixture or any number of drugs asdesired. The therapeutic agent 330 may be introduced into the cavity 110in any number of ways. For example, the insert which erodes to form thecavity may comprise the therapeutic agent 330. Alternatively or incombination, the therapeutic agent 330 may be a coating on the insert.The therapeutic agent 330 may remain in the cavity following dissolutionof the insert. Alternatively or in combination, the therapeutic agent330 may be introduced into the cavity 110 following erosion of theinsert or via the external solution in which the lens 100 is stored. Theexternal solution may be an aqueous solution 204 containing thetherapeutic agent 330 such that as the internal cavity 110 comes toequilibrium with the external storage solution, the therapeutic agent330 diffuses across the lens body 120 into the cavity 110. The storagesolution may be of such a concentration, temperature, composition, orany comparable parameter that the rate of diffusion can be controlled toload the cavity 110 with the desired amount of therapeutic agent 330.The therapeutic agent 330 may also be introduced into the cavity 110through any technique known to those skilled in the art. The therapeuticagent 330 may be delivered to the eye when the lens 100 is being wornvia diffusion. The therapeutic agent 330 may diffuse across a posteriorside 106 of lens 100 to the eye. The posterior side 106 of the lens 100may act as a rate control structure. For example, the posterior side 106of the lens 100 may comprise a thickness 107. The thickness 107 may bevaried in order to control the diffusion rate 332 of the therapeuticagent 330 through the posterior side 106 of the lens 100 onto thesurface of the eye.

FIG. 18 shows a contact lens 100 with a cavity 110 near the anteriorlens surface 137 configured for therapeutic agent delivery to the eye ofthe wearer. Placement of the cavity 110 near the anterior lens surface137 may be useful to achieve the desired diffusion behavior. Placementof the cavity 110 near the posterior lens surface 136 may be useful toachieve the desired refractive behavior and may be situated in such away to be outside of the optical zone. The cavity 110 may be continuouswith one or more other cavities in the lens configured to delivertherapeutic agents, aid in vision, or any other purpose disclosedherein. The cavity 110 may comprise a therapeutic agent 330. Thetherapeutic agent 330 may comprise any of the drugs or therapeuticagents described herein. The therapeutic agent 330 may comprise aplurality of drugs, for example a mixture or any number of drugs asdesired. The therapeutic agent 330 may be introduced into the cavity 110in any number of ways. For example, the insert which erodes to form thecavity may comprise the therapeutic agent 330. Alternatively or incombination, the therapeutic agent 330 may be a coating on the insert.The therapeutic agent 330 may remain in the cavity following dissolutionof the insert. Alternatively or in combination, the therapeutic agent330 may be introduced into the cavity 110 following erosion of theinsert or via the external solution in which the lens 100 is stored. Theexternal solution may be an aqueous solution 204 containing thetherapeutic agent 330 such that as the internal cavity 110 comes toequilibrium with the external storage solution, the therapeutic agent330 diffuses across the lens body 120 into the cavity 110. The storagesolution may be of such a concentration, temperature, composition, orany comparable parameter that the rate of diffusion can be controlled toload the cavity 110 with the desired amount of therapeutic agent 330.The therapeutic agent 330 may also be introduced into the cavity 110through any technique known to those skilled in the art. The therapeuticagent 330 may be delivered to the eye when the lens 100 is being wornvia diffusion. The therapeutic agent 330 may diffuse across a posteriorside 106 of lens 100 to the eye. The posterior side 106 of the lens 100may act as a rate control structure. For example, the posterior side 106of the lens 100 may comprise a thickness 107. The thickness 107 may bevaried in order to control the diffusion rate 332 of the therapeuticagent 330 through the posterior side 106 of the lens 100 onto thesurface of the eye.

FIG. 19 shows a contact lens 100 with a cavity 110 outside the opticalzone 170 configured for therapeutic agent delivery to the eye of thewearer. The cavity 110 may comprise a therapeutic agent 330. Thetherapeutic agent 330 may comprise any of the drugs or therapeuticagents described herein. The therapeutic agent 330 may comprise aplurality of drugs, for example a mixture or any number of drugs asdesired. The therapeutic agent 330 may be introduced into the cavity 110in any number of ways. For example, the insert which erodes to form thecavity may comprise the therapeutic agent 330. Alternatively or incombination, the therapeutic agent 330 may be a coating on the insert.The therapeutic agent 330 may remain in the cavity following dissolutionof the insert. Alternatively or in combination, the therapeutic agent330 may be introduced into the cavity 110 following erosion of theinsert or via the external solution in which the lens 100 is stored. Theexternal solution may be an aqueous solution 204 containing thetherapeutic agent 330 such that as the internal cavity 110 comes toequilibrium with the external storage solution, the therapeutic agent330 diffuses across the lens body 120 into the cavity 110. The storagesolution may be of such a concentration, temperature, composition, orany comparable parameter that the rate of diffusion can be controlled toload the cavity 110 with the desired amount of therapeutic agent 330.The therapeutic agent 330 may also be introduced into the cavity 110through any technique known to those skilled in the art. The therapeuticagent 330 may be delivered to the eye when the lens 100 is being wornvia diffusion. The therapeutic agent 330 may diffuse across a posteriorside 106 of lens 100 to the eye. The posterior side 106 of the lens 100may act as a rate control structure. For example, the posterior side 106of the lens 100 may comprise a thickness 107. The thickness 107 may bevaried in order to control the diffusion rate 332 of the therapeuticagent 330 through the posterior side 106 of the lens 100 onto thesurface of the eye.

The posterior side of the lens may comprise a thickness defined betweena posterior surface of the contact lens body and a posterior surface ofthe inner cavity within a range of about 10 microns to about 200microns, or within a range bounded by any two thicknesses therebetween.The posterior side of the lens may comprise a thickness within a rangeof about 10 microns to about 150 microns, 10 microns to about 100microns, within about 10 microns to about 50 microns, or within a rangeof about 10 microns to about 25 microns. The posterior side of the lensmay comprise a thickness within a range of about 25 microns to about 200microns, about 25 microns to about 150 microns, about 25 microns toabout 100 microns, or within about 25 microns to about 50 microns. Theposterior side of the lens may comprise a thickness within a range ofabout 50 microns to about 200 microns, about 50 microns to about 150microns, about 50 microns to about 100 microns. The posterior side ofthe lens may comprise a thickness within a range of about 100 microns toabout 200 microns, about 100 microns to about 150 microns. The posteriorside of the lens may comprise a thickness within a range of about 150microns to about 200 microns.

The anterior side of the lens may comprise a thickness defined betweenan anterior surface of the contact lens body and an anterior surface ofthe inner cavity within a range of about 10 microns to about 200microns, or within a range bounded by any two thicknesses therebetween.The anterior side of the lens may comprise a thickness within a range ofabout 10 microns to about 150 microns, 10 microns to about 100 microns,within about 10 microns to about 50 microns, or within a range of about10 microns to about 25 microns. The anterior side of the lens maycomprise a thickness within a range of about 25 microns to about 200microns, about 25 microns to about 150 microns, about 25 microns toabout 100 microns, or within about 25 microns to about 50 microns. Theanterior side of the lens may comprise a thickness within a range ofabout 50 microns to about 200 microns, about 50 microns to about 150microns, about 50 microns to about 100 microns. The anterior side of thelens may comprise a thickness within a range of about 100 microns toabout 200 microns, about 100 microns to about 150 microns. The anteriorside of the lens may comprise a thickness within a range of about 150microns to about 200 microns.

The anterior thickness of the lens may be less than the posteriorthickness of the lens. The posterior thickness of the lens may be lessthan the anterior thickness of the lens. The anterior thickness of thelens may be substantially the same as the posterior thickness of thelens. The anterior side of the lens may have a uniform thickness or anon-uniform thickness. The posterior side of the lens may have a uniformthickness or a non-uniform thickness.

The lens may comprise a total thickness defined between an anteriorsurface of the contact lens body and a posterior surface of the contactlens body within a range of about 20 microns to about 400 microns, orwithin a range bounded by any two thicknesses therebetween. The totalthickness of the lens may be within a range of about 50 microns to about400 microns, about 80 microns to about 350 microns, about 80 microns toabout 250 microns, about 100 microns to about 300 microns, about 100microns to about 400 microns, about 200 microns to about 400 microns,about 200 microns to about 300 microns, about 300 microns to about 400microns.

The cavity may comprise a thickness defined between an anterior surfaceof the internal cavity and a posterior surface of the internal cavitywithin a range of about 0.5 microns to about 200 microns, or within arange bounded by any two thicknesses therebetween. The cavity maycomprise a thickness within a range of about 5 microns to about 150microns, about 15 microns to about 100 microns, about 15 microns toabout 50 microns, about 25 microns to about 200 microns, about 50microns to about 100 microns.

Experimental

The inventors conducted bench experiments and calculations to develop anaccommodating contact lens. Development of the accommodating contactlens with an embedded cavity utilized a simulation and analysis approachbased on COMSOL, MATHCAD, SOLIDWORKS and MATLAB. Table 3 shows thedesign parameters used in Example 1.

TABLE 3 Dimensions of the accommodating contact lens (Example 1)Anterior Posterior Radius of Radius of Center Refractive CurvatureCurvature Thickness Diameter Index (mm) (mm) (microns) (mm) Lens 1.418.85 8.6 100 — Cavity 1.34 8.75 8.7 50 3.6

It was found that the cavity developed a power of −0.70 D, since therefractive index of the cavity was less than that of the substrate. Thepower of the overall lens was simulated to be—0.93 D.

Table 4 shows the design parameters used in Example 2.

TABLE 4 Dimensions of an accommodating contact lens (Example 2).Anterior Posterior Radius of Radius of Center Refractive CurvatureCurvature Thickness Diameter Index (mm) (mm) (microns) (mm) Lens 1.418.85 8.6 200 — Cavity 1.34 8.75 8.0 50 3.6

It was found that the cavity developed a power of 0.0 D, since therefractive index of the cavity was less than that of the substrate. Thepower of the overall lens was simulated to be—0.23 D.

Lens power was simulated as a function of the depth of the cavity withinthe lens and also as a function of the posterior radius of curvature ofthe cavity.

FIG. 20 shows simulated results of lens power as a function of theposterior radius of curvature of the cavity, in accordance withembodiments.

Spherical lens power (measured in D) was simulated with respect to theposterior radius of curvature (roc) of the cavity (measure in mm). Rocvalues from 8.7 to 6.9 mm induced spherical lens powers varying between−1 D and 1.25 D. Lens power was strongly dependent on the posteriorcurvature of the cavity. Curvature may be controlled by providing theinsert as a curved film with a specified radius of curvature.

FIG. 21 shows simulated results of lens power as a function of cavityposition within the lens, in accordance with embodiments.

Spherical lens power was simulated as a function of a cavity position inthe lens with respect to the lens anterior surface (distance measured inum). Cavity positions between 100 um and 1900 um were simulated to givespherical lens powers between −0.25 D and −0.2 D. It was found that thelens power was not very sensitive to the depth of the cavity in thelens, providing some relief on the tolerance of the z axis placement ofthe cavity inside the lens molding cavity.

It was further assumed that the tensile modulus of the hydrogelcomprising the lens was 1 MPa, bulk modulus of saline was 2.08 GPA anddensity was 1000 Kg/m³. Simulations of inflation were performed foreyelid tensions from 10 Pa, 50 Pa, 250 Pa and 1000 Pa.

TABLE 5 provides the results of the simulations. Parameter ValuesPressure Applied by Lower 10 50 250 1000 Eyelid (Pa) Effective Pressurein Cavity (Pa) 7 34 171 427 Cavity Volume (mm3) 1.543 1.543 1.543 1.543Fluid Volume Transferred (nL) 12 61 301 748

The sag profile obtained through simulation shows that the enhanced sagprofile is essentially spherical, with an add power of 3.0 D beingachieved at 50 Pa of eyelid pressure.

Several lenses were cast for each of Examples 1 and 2. The insert wasmade of a biocompatible soluble uncross-linked polyvinyl alcohol, calledSolublon®, grade GA. This particular grade of Solublon® is soluble incold water and studies of dissolution of Solublon® in water at roomtemperature showed that the polymer film dissolved without initiallyswelling, which is helpful because swelling of the insert prior to itsdissolution may cause the cavity to expand, which may result infracture. Other biocompatible water soluble polymers that may be used inaccordance with embodiments include polyvinyl alcohol, polyvinylacetate, polyethylene oxide, propylene oxide, copolymers of ethylene andpropylene oxides (Pluronic acids), poly vinyl pyrollidone, polyethyleneimines, polyacrylamides, and polysaccharides.

The insert may be made from a single material or a blend of polymerswith different dissolution rates, in order to control the rate offormation of the cavity through dissolution of the material comprisingthe insert. Solutes may be dissolved or blended into the materialcomprising the insert prior to forming the insert. The solutes may havea molecular weight such that diffusion of the solutes through theboundary of the cavity and permeation through the lens body may becontrolled.

The insert may be formed using methods including thermoforming,compression molding, or solution casting. The surface of the insert maybe coated to alter and control the diffusion of solvent and othersolutes across the boundary of the cavity. For example, the insert maybe coated with a solution of cross-linking agent or a photocuringcatalyst in order to develop a gradient of cross-linking densities andcure rates starting at the surface of the insert.

In one embodiment, an accommodating contact lens was cast from ahydrogel of water content 32%, formed by photo-polymerizing andcross-linking a zero expansion formulation. Alternative embodiments mayinclude a lens cast from a hydrogel of water content within a range ofabout 28% to 65%. The polymerized lens material may comprise one or moreof a monomer or an oligomer, a homopolymer, or a low expansion polymer.Other polymers may be used in accordance with embodiments, including asilicone hydrogel copolymer. Curing methods are not limited tophoto-polymerization and may include any appropriate method for thechosen contact lens polymer and may include catalysts or reactants.

FIGS. 22A-22B show casting cups used to cast an accommodating contactlens, in accordance with embodiments. In the present embodiment, themonomer was placed in a mold cavity formed as shown in FIGS. 22A-22B. Abenefit of the insert described herein is that previously known moldsmay also be used to cast a lens comprising an internal cavity.

The lower mold that forms the anterior surface of the lens was held by afixture. A small amount (˜10 uL) of monomer was delivered into the lowercup from a syringe that was lowered by a fixture along the center of themold, under nitrogen gas. The resin was partially cured, then theinsert, held at the tip of a vacuum forceps was vertically lowered intothe resin layer in the lower cup along the center of the lower mold. Thefixture was subsequently lifted up, then used to lower the syringefilled with additional monomer in order to deliver the rest of themonomer required to form the lens. The syringe was lifted back up afterdelivering monomer, and the same fixture was used to bring the uppermold down along the same vertical (z) axis. The two molds were gentlyengaged and pressed shut. The design of the mold rims and theirdiameters are critical in ensuring that the molds form a closed cavitythrough a press-fit, without disturbing the surface of the monomer orforming bubbles.

The mold assembly was then cured under long wave length UV light (390nm), until polymerization was complete. The molds were then opened, andthe lens adhering to the lower mold was then immersed in saline andsonicated to de-mold the lens. The de-molded lens was hydrated for aperiod between 2-6 hours, and then washed in a dilute (0.01 M) NaOH indeionized water for a period ranging from 2-6 hours. The lens was thenplaced back into saline and hydrated by immersing in saline for a periodfrom 6-24 hours. The saline solution was replenished at least oneadditional time before hydration was complete.

FIGS. 23A-23B shows progress of hydration and gradual dissolution of theinsert 140 to form the cavity 110.

FIG. 23A shows a contact lens 100 after two hours of hydration in 0.9%saline and 1.5 hours of sonication. The contact lens 100 has begun tohydrate with the insert 140 still visible inside said lens.

FIG. 23B shows a contact lens 100 after overnight hydration whereby thelens 100 has become fully hydrated and the insert 140 has dissolved toform cavity 110.

FIG. 24 shows a fully hydrated soft contact lens 100 under bright fieldmicroscopy. The hydrated lens 100 comprises an embedded cavity 110remaining where the insert 140 was, following gradual dissolution of theinsert.

Table 6 reports data on the thickness of various layers in theaccommodating contact lens with an embedded cavity.

TABLE 6 Lens thickness profiles. Thickness Layer (microns) AnteriorHydrogel Layer 64 Cavity (Insert Thickness: 75 microns) 88 PosteriorHydrogel Layer 82 Total Lens Thickness (As Sum of All Layers) 234 TotalLens Thickness (As Measured) 215

The target thickness of the accommodating contact lens was 200 microns,so there is satisfactory agreement between target and actualthicknesses.

FIG. 25 shows an accommodating soft contact lens comprising a cavity oneye (Example 3). The cavity was formed by the dissolution and diffusionof a Solublon®, grade GA, insert through the lens body materialcomprising HEMA. The cavity is shaped similarly to the embodiment ofFIG. 12 with an inner optical chamber 114, a first outer chamber 116 a,a second outer chamber 116 b, and one or more channels there between(not labeled), as shown in FIG. 12. The chambers 114, 116 a, 116 bboundaries of the cavity are barely visible on the eye, indicating ahigh level of clarity and optical quality of the lens after hydrationand dissolution of the insert material.

FIG. 26 shows an accommodating soft contact lens comprising an inkedcavity on eye (Example 4). The lens was formed similarly to the lens inFIG. 25 but a dye has been added to the cavity to increase contrast andallow for direct visualization of the cavity on the eye. Some artifactsof the molding process can be seen (such as the bubbles near theperipheral chambers 116 a, 116 b). Based on the teachings providedherein, a person of ordinary skill in the art can construct lenseswithout such artifacts, and this image was provided to show structuresof the contact lens that would not normally be visible. The centralreservoir 114 and outer chambers 116 a, 166 b are well-situated on theeye to provide accommodation with changes in gaze. The inner (central)reservoir 114 lies over the optical center portion of the eye. Rapid,repeated blinking did not disturb the location of the cavity relative tothe optical portion of the eye, indicating that the lens is stablylocated on the surface of the eye. The first outer (peripheral) chamber116 a and the second outer chamber (116 b) are located above the lowerlid of the eye and therefore does not provide any added optical power tothe inner optical chamber 114 when the eye and contact lens are in a farvision configuration. Alterations of the gaze may engage the outerchambers 116 a, 116 b with the lower eyelid to provide intermediate andnear vision correction as described herein.

FIG. 27 shows a lens power measurement test for an accommodating softcontact lens with an inflated inner chamber as described herein. Thelens 100 was formed similarly to the lenses in examples 3 and 4described previously. Light in the form of a grid of dots was passedthrough lens 100 in order to determine the power of the lens 100 atvarious locations within the lens body. The dot size inside the lens wascompared to the dot size outside the lens in order to determine theoptical power changes of the lens, with the dots size outside the lenscorresponding to 0 D of optical power. The ratio of dot sizes andspacing of the dots from each other is directly related to the opticalpower. For example, if a dot inside the lens is twice the size of a dotoutside the lens, then the power of the lens is 2 D. If a dot inside thelens is half the size of a dot outside the lens, the power of the lensis −2 D. Non-spherical dots indicate prism in the lens, which can berelated to astigmatism of the lens.

The lens 100 comprises distinct zones of optical power. The center ofthe lens comprises an optical zone 170 as described herein. The opticalzone 170 is substantially circular and has a diameter of about 6 mm.Around the optical zone 170 is a transition zone 172 which appears assquashed dots that may indicate prism. The next ring zone comprises anouter near vision zone 176 which may comprise a prism ballast tostabilize the lens, for example with reference to the rotationallystable contact lens design of FIG. 6. The outer edge of the lens 102comprises blend zones 174 which lose focus and optical power compared tothe central regions of the lens. The dot size in the outer near visionzone 176 is about half the size of the dots outside the lens, indicatingthat the outer near vision zone176 has an optical power of about −2 D.The dots inside the optical zone 170 are spaced similarly to the dotsoutside the lens and correspond to an optical power of about 0 D, whichis about +2 D as compared to the dots in the outer near vision zone 176.The optical power of about OD with inflation would allow a near sightedwearer to see up close. Thus the lens with the inflated inner opticalchamber is a multifocal lens with both near and far vision zones with atransition zone 172 extending therebetween and a well formed centraloptical zone 170. When the chamber deflates, the optical power of theinner optical zone would change to about −2 D and provide far visioncorrection with the central optical zone 170. Although the lens is shownwith reference to a spherical lens to correct −2 D of sphericalrefractive power, other lenses with other optical powers and astigmatismcorrection can be manufactured and tested as described herein.

The lens comprises a low amount of astigmatism or prism in thetransition zone 172. Prism in the transition zone may be related to therate of change in the radius of curvature (roc) of the different lensregions. A ballast lens design may provide a reduced rate of change ofthe roc leading to reduced differences between radial and sagittalcurvature one moves radially outward from the center of the lens. Thelens may be substantially radially symmetric as defined by a ballastedback curve and the insert used to form the cavity. The insert may forexample have a tapered edge in order to decrease the rate of change ofthe roc and inhibit the formation of prism near the boundary of thecavity. Alternatively or in combination, the amount of prism in the lensmay be reduced by the formation of a graded refractive index with arefractive index gradient extending between the cavity and lens body asdescribed herein. A refractive index gradient may inhibit prism relatedto an abrupt change in refractive index at the boundary of the cavity.

FIGS. 28A-28B show the accommodating soft contact lens of FIG. 26 oneye. Optical coherence tomography (OCT) was used to generate across-sectional image of the lens and surface of the eye along the lineindicated in FIG. 28A. FIG. 28B shows an OCT cross-section of thecontact lens 100 with the thicknesses of various parts of the lens 100highlighted. The cavity 110 was formed with a thickness of about 220 um,which corresponded to the thickness of the insert used to form thecavity 110. The cavity 110 is defined as the space between a posteriorside 106 of the lens 100 and an anterior side 104 of the lens 100. Inthis embodiment, the thickness of the anterior side 104 of the lens 100is about 330 um and the thickness of the posterior side 106 of the lens100 is about 100 um. The lens 100 sits atop the cornea of the eye 290which has a thickness of about 550 um. In many embodiments, thethickness of the anterior hydrogel layer 104 may be different from thethickness of the posterior hydrogel layer 106 of the lens 100. Thethickness of the anterior surface 104 of the lens may be more than thethickness of the posterior surface 106 of the lens, as shown in FIG.28B, for example to inhibit distortion of the anterior surface of thelens when the contact lens is in a presbyopia-correcting near visionconfiguration and the inner optical chamber of the cavity is inflated toincrease optical power.

The thickness of the anterior surface 104 of the lens may be less thanthe thickness of the posterior surface 106 of the lens, for example tofacilitate deflection of the anterior surface 104 of the lens when thecontact lens is in a presbyopia-correcting near vision configuration andthe inner optical chamber of the cavity 110 is inflated to increaseoptical power. The thickness of the anterior surface 104 of the lens maybe less than the thickness of the posterior surface 106 of the lens suchthat inflation of the inner optical chamber of the cavity 110 leads todeflection of the anterior and posterior surfaces 104, 106, wherein theanterior surface 104 deflects more than the posterior surface 106 withinflation to correct presbyopia. In many embodiments, the thickness ofthe anterior side 104 of the lens is at least about 50 microns. In manyembodiments, the thickness of the anterior side 104 of the lens is nomore than about 100 microns. In many embodiments, the thickness of theposterior side 106 of the lens is at least about 100 microns. In manyembodiments, the thickness of the posterior side 106 of the lens is nomore than about 200 microns.

FIG. 29 shows an accommodating soft contact lens comprising a cavitywith central bulging on eye (Example 5). The lens was formed similarlyto the lenses in examples 3 and 4. A Solublon® was used to form a cavityinside a lens material comprising HEMA. Upon hydration of the lens, theSolublon® insert was degraded and the soluble components were allowed todiffuse out of the lens body to form the cavity. Solublon® comprises acopolymer of PVA. As described herein, PVA polymer chains may retainsome amount of residual acetate, for example within a range from about1% to about 20% depending of the extent and efficiency of hydrolysis ofPVAc. At least a portion of the solubilized Solublon® material maycomprise vinyl groups comprising acetate which is only partially solubleor insoluble and unable to diffuse through the pores of the HEMA lensbody as described herein. The residual insert material may lead tochanges in osmotic pressure in the cavity and expansion of the cavity aswater flows into the cavity during hydration to create a bulge 290 asshown in example 5. The extent of bulging and the osmotic pressure ofthe cavity may be adjusted by changing the acetate content in the PVAinsert material. The pressure of the cavity was relieved after about 1to 2 days and may have contributed to a refractive index gradient withinthe cavity, which may in turn contribute to the low prism in the opticalzone observed in FIG. 27, as described herein. The insert material canbe configured in many ways as described herein in order to providelimited amounts of swelling that inhibit distension of the contact lensbody defining the cavity during hydration, and which provide suitableosmolality of the cavity as described herein.

FIGS. 30A-30B show the accommodating soft contact lens of FIG. 29 oneye. OCT was used to generate a cross-sectional image of the lens andsurface of the eye along the line indicated in FIG. 30A. FIG. 30B showsan OCT cross-section of the contact lens 100 with the thicknesses ofvarious parts of the lens 100 highlighted. The cavity 110 was formedwith a thickness of about 220 um, which corresponded to the thickness ofthe insert used to form the cavity 110. In this embodiment, degradationof the Solublon® within the cavity during hydration increased theosmotic pressure of the inner optical chamber 114, as described herein,and resulted in an osmotic pressure bulge with a thickness of about 2 mmbetween inner anterior and posterior surfaces 104, 106 of the lensdefining the cavity. The bulge 290 stretched the lens anterior side 104to about 20 um thick near the thickest part of the bulge 290. Theosmotic pressure relieved itself after 1-2 days and the bulge 290receded to form the cavity 110 comprising a refractive index gradientwith low prism in the optical zone as described herein.

Several lenses were cast for each of Examples 3, 4, and 5. An insert foreach lens was made of a biocompatible soluble uncross-linked polyvinylalcohol, called Solublon®, grade GA, as described herein. Solublon®grade GA is a copolymer of vinyl alcohol and vinyl acetate and dissolvesrapidly in cold water. Other biocompatible water soluble polymers thatmay be used in accordance with embodiments include polyvinyl alcohol,polyvinyl acetate, copolymers of vinyl acetate and vinyl alcohol (e.g.poly[(vinyl alcohol)-co-(vinyl acetate)] or PVA/Ac), polyethylene oxide,propylene oxide, polyethylene glycols (PEGs) in the molecular weightrange of about 600 g/mol to about 6000 g/mol, copolymers of ethylene andpropylene oxides (Pluronic acids), poly vinyl pyrollidone, polyethyleneimines, polyacrylamides, and polysaccharides. The water soluble insertmay comprise hydrophilic ionic polyacrylates or polymethacrylates orcopolymers thereof. The carboxylate groups pendant on the polymer can beionized, binding to divalent or trivalent metal ions as counter-ions,and these carboxylate groups may also be used to form water solublepolymer films. Metal ions may form ionic cross-links that are watersensitive, and are opened in water of a particular pH, depending on theionization constants of the polymer bound carboxylate groups, forexample. The insert was shaped to create a cavity with an inner opticalchamber, a first outer chamber, a second outer chamber, and one or morechannels there between, as shown in FIG. 12.

FIG. 31 shows a method of manufacturing a contact lens comprising acavity, in accordance with embodiments.

At Step 2301, an erodible insert material may be provided. The erodibleinsert material may be any of the insert materials described previouslyherein. The insert material may be formulated such that the insert cansurvive heat or UV curing processes.

At Step 2302, the insert material may be shaped to form the insert.Shaping may comprise one or more optional steps which may includeheating (Step 2303), punching out a shape from the insert material (Step2304), or providing a curvature to the insert material (Step 2305). Forexample, a desired shape may be punched out of a solid insert materialthen heated while laying on a sphere with the desired lens base curve.

At Step 2306, a small amount of lens pre-polymer may be provided to amold.

At Step 2307, the pre-polymer may be partially cured to form a bed forthe insert.

At Step 2308, the shaped, solid, erodible insert may be provided to thepartially-cure polymer.

At Step 2309, the insert may be optionally secured to thepartially-cured polymer base by providing a drop of polymer to theinsert and flash curing it into position.

At Step 2310, additional pre-polymer may be added to the mold toencapsulate the insert.

At Step 2311, the lens may be shaped. Shaping the lens may comprise oneor more steps including cutting (Step 2312) or molding (Step 2313).

At Step 2314, the lens may be hydrated.

At Step 2315, the insert may dissolve.

Hydration of the lens and degradation of the insert material may occurat different rates. For example, the lens material may hydrate fasterthan the insert material dissolves and thereby restrict the expansion ofthe lens material, for example HEMA, into the cavity. The lens materialmay instead expand outward to form a full-sized contact lens with littleto no aberrations or disruptions to the cavity.

At Step 2316, at least a portion of the insert material may diffusethrough the lens body.

At Step 2317, at least a portion of the insert material may remaininside the cavity.

The insert material may for example comprise Solublon® as describedherein. Degradation of the Solublon® material into its components maygenerate a plurality of polymer chains. At least a portion of thepolymer chains may comprise acetate which is hydrophobic and does notdissolve in water. At least a portion of the polymer chains may comprisealcohol which is hydrophilic and does dissolve in water. The dissolvedcomponents may diffuse through the hydrophilic lens material, forexample HEMA, and be released from the cavity. When the concentration ofacetate on each polymer chain is high enough, for example more thanabout 3% or 4% of pendant groups, the hydrophobic moieties on thepolymer chains may be repelled by the HEMA, resulting in a residualamount of insert material inside the cavity after hydration of the lens.The residual insert material may lead to changes in osmotic pressure inthe cavity and expansion of the cavity as water flows into the cavityduring hydration. The pressure of the cavity may be relieved when thecavity is in balance with the HEMA. The composition of the insertmaterial may be modified to adjust the amount of osmotic pressure and/orresidual material of the cavity, for example by modifying the ratio ofhydrophobic pendant groups to hydrophilic pendant groups of the polymer.

The insert may for example comprise a substance, for example across-linking agent, which may be used to modify the characteristics ofthe cavity. The density of the lens material may be modified dependingon the desired lens characteristics. The cross-link density of the lensmaterial may be modified depending on the desired lens characteristics,for example to alter pore size of the lens.

Although the steps above show a method of providing a contact lens witha cavity using an erodible insert in accordance with embodiments, aperson of ordinary skill in the art will recognize many variations basedon the teachings described herein. The steps may be completed in adifferent order. Steps may be added or deleted. Some of the steps maycomprise sub-steps. The steps may be repeated to provide a contact lensor an insert as described herein.

FIGS. 32-33 show diffusion of a low molecular weight dye out of the lenscavity. A lens 100 comprising a cavity 110 was formed as describedherein and a low molecular weight dye was added to the cavity 110 to actas a surrogate for the insert material in order to monitor the effect ofmolecular size of the insert material on the rate ofdiffusion/extraction out of the lens body. The dye had a molecularweight of 242 g/mol and was water soluble. The lens comprising the dyewas immersed in a PBS hydrating solution 340 and diffusion from thecavity was monitored by observing the change in the color of thesolution surrounding the lens. FIG. 32 shows the lens 100 prior toimmersion in the extraction or hydrating solution 340 (e.g. at 0 hours).The cavity 110 appears dark due to the presence of the dye. FIG. 33shows the lens 100 after 24 hours incubation in the extraction solution340. The dye diffused out of the cavity 110 into the extraction solution340, thus the extraction solution 340 appears darker in FIG. 33 than inFIG. 32 due to the presence of the dye.

FIGS. 34A-34F show diffusion of two different molecular weight dyes outof lens cavities. Lenses 100 a and 100 b were imbued with low molecularweight dyes within their cavities 110 a and 110 b, respectively, and therate of diffusion was qualitatively assessed by monitoring the color ofthe extraction solution 340 as described in FIGS. 33A-33B. FIGS. 34A-34Cshow a lens 100 a comprising a dye with a molecular weight of 242 g/molwithin cavity 110 a. FIG. 34A shows the lens prior to incubation in thePBS extraction solution 340. FIGS. 34B and 34C show the lens 100 a andextraction solution 340 after 5 hours incubation. The extractionsolution 340 as well as the lens body have begun to darken as the dyehas diffused through the lens body and into the extraction solution.FIGS. 34D-34F show a lens 100 b comprising a dye with a molecular weightof 872 g/mol within cavity 110 b. FIG. 34D shows the lens prior toincubation in the PBS extraction solution 340. FIGS. 34E and 34F showthe lens 100 b and extraction solution 340 after 5 hours incubation.Most of the dye remained in the cavity 110 b after 5 hours, thus theextraction solution 340 had little color change. The results of FIGS.34A-34F show that the size of the insert material may affect the rate atwhich the insert material is able to diffuse out of the lens body toform the cavity. Extraction of the insert material from the lens mayalternatively or in combination depend on the permeability of the lensmaterial, the polarity of the lens material, and/or the polarity of theinsert material.

Extraction of insert material may be aided by altering the composition,temperature, and/or movement of the extraction solution 340. Some of thepossible combinations of these parameters were tested. Salineconcentrations between about 0.9% and about 25% were tested, as well astemperatures between about 25° C. to about 65° C. Saline was tested incombination with isopropanol ad other organic solvents. In someexperiments, the extraction was carried out by alternating saline andsaline with organic solvents at different time intervals to generate achemical pump effect to extract the insert material from the cavity. Amedium-pressure circulating machine was used in multiple experimentswith different solvents and different temperatures to further aid inextraction of the insert material. It was found that organic solvents incombination with saline could accelerate the extraction process of theinsert materials compared to saline alone. The use of solventcirculation was able to improve the extraction process. Extraction atelevated temperatures in combination with solvent circulation providedaccelerated extraction.

A number of potential insert materials were tested for their ability toreadily diffuse out of the lens body including PEG (at multipledifferent molecular weights), Methocel™ E6 (a cellulose-like material)at 50,000 g/mol, poly sodium methacrylate (at multiple differentmolecular weights), PVA/Ac (at multiple different molecular weights),sugars (including isomalt, sucrose, and glucose), and salts (includingsodium chloride). The insert materials were tested for the ability toform a thin film-like insert (for example by spreading a thin layer of ahydrated insert material and allowing it to form a dry film throughevaporation), the ability to diffuse through the lens (by measuring theconcentration of the insert material in the extraction solution), and/orflexibility. The lenses were monitored for cavity formation with orwithout the formation of a bulge. In some instances, an insert materialwhich forms thin, flexible film-like inserts that readily diffuse out ofthe lens body without forming a bulge may be desirable.

FIGS. 35A-35C show sucrose films generated using a cast-free meltingmethod. Heated liquid sucrose was spread on a flexible surface, such asa silicone sheet, using an applicator blade at elevated temperature. Thesucrose was cooled to form a 22 um thick film-like sheet which could beused to form inserts of a desired shape and size. The sucrose film wasremoved from the silicone sheet by bending the sheet to release the filmand allow it to be removed. FIG. 35A shows a sucrose insert film 140 aon a silicone sheet. FIG. 35B shows the sucrose film 140 a of FIG. 35Abeing removed from the silicone sheet with the aid of a thin removaltool 350. FIG. 35C shows the sucrose film 140 a of FIG. 35A afterremoval from the silicone sheet to form a free-standing sucrose film 140a. Experiments using solvent film casting were not successful in formingfilms.

FIGS. 36A-36C show the flexibility of various sugar-based insert films.FIG. 36A shows the flexibility of a 22 um sucrose film. FIG. 36B showsthe flexibility of a 55 um glucose film. FIG. 36C shows the flexibilityof a 50 um isomalt film. Each of the sugar films were relativelyflexible and were able to be curved or bent. The flexibility of thesugar films may depend on the moisture and relative humidity of thesurroundings. The flexibility of the sugar films may be altered toprovide processible inserts such that the inserts may be sized andshaped as desired.

FIGS. 36D-36F show the results of cavity formation of lenses comprisingvarious sugar-based inserts. Backlighting was applied for bettervisualization of the cavity 110 within the lens 100. Each of the lenses100 were hydrated to dissolve the inserts and form cavities 110. FIG.36D shows a cavity 110 formed by a 22 um sucrose insert after 24 hoursof hydration with an extraction solution as described herein. The cavity110 was formed without noticeable swelling or bulge formation. FIG. 36Eshows a cavity 110 formed by a 55 um glucose insert after 24 hours ofhydration. The cavity 110 was formed with a slight amount of noticeableswelling. FIG. 36F shows a cavity 110 formed by a 50 um isomalt insertafter 24 hours of hydration. The cavity 110 was formed with a slightamount of noticeable and acceptable swelling. The concentration ofmaterial in the extraction material can be measured in many ways, forexample with liquid chromatography-mass spectroscopy (LC-MS), gaschromatograph-mass spectroscopy (GC-MS), gas chromatography-flameionization detection (GC-FID) and other methods of detecting materialknown to one of ordinary skill in the art

FIG. 37A shows a 200 um thick insert 140 made of sodium chloride. Theinsert 140 was formed by compressing a fine sodium chloride solid undera high load using a 2 ton press. In early experiments, the salt waferswere formed with a tool with a patterned surface which left imprintedpatterns 360 on the inner walls of the lens cavity 110 as shown in FIG.37B. A piece of stainless steel with a mirrored surface was used toovercome the issue of lens patterning. FIGS. 37B-37D show the results ofcavity 110 formation of three different lenses 100 comprising 200 umsodium chloride inserts. Backlighting was applied for bettervisualization of the cavity 110 within the lens 100. The cavities 140were formed after 24 hours of hydration without noticeable bulgeformation. FIG. 37C shows a lens 100 with a cavity 110 without bulging.FIG. 37D shows a lens 100 with a cavity 110 comprising an entrapped airbubble 370 imperfection. Other salts, for example less crystallinesalts, may also be used as an insert material.

Experiments with Methocel™ E6 showed that Methocel™ E6 was able to formthin film-like inserts. Lenses cast around the insert were hydrated andlarge bulges were observed upon hydration. The insert material did notdiffuse out the cavity effectively, perhaps because of its highmolecular weight of 50,000 g/mol.

Experiments with poly sodium methacrylates showed varying abilities toform thin film-like inserts. Higher molecular weight poly sodiummethacrylate at 12,000 g/mol formed good films while lower molecularweight poly sodium methacrylate at 1,200 g/mol crystalized during theevaporation process and did not form film-like inserts. Lens cast aroundthe 12,000 g/mol poly sodium methacrylate formed large bulges uponhydration within a short period of about 1-2 hours. The affinity of thepoly sodium methacrylate to water may have led to the formation ofbulges, suggesting that insert materials with high water content may beavoided if bulging is not desired.

Experiments with PVA/Ac at 12,000 g/mol and 6,000 g/mol were tested andformed good film-like inserts. Lenses cast around the 12,000 g/molinserts formed bulges after 24 hours of hydration and no PVA/Ac materialwas detected in the extraction solutions, saline or isopropanol, tested.Lenses cast around the 6,000 g/mol inserts had minimal to no bulgeformation.

In another experiment, a mixture of 70% PVA/Ac at 6000 g/mol and 30%polyethylene glycol was dissolved in water and spread on a flexiblesurface to dry. The PEG was added to act as a plasticizer. The water wasevaporated to form a thin film-like insert material. The insert materialwas highly flexible, not sticky, and strong. The insert was not brittleand had good tensile strength. The insert was capable of being picked upwithout breaking, supporting its own weight as a free-standing insert.The insert was flexible with a bend radius of curvature of about 7 mm.

Additional experiments can be conducted with dark field microscopy todetect an interface between a first portion of the contact lens formedwith partial polymerization bonded to a second portion of the of thecontact lens formed by additional polymerization of the first portion inthe presence of the precursor material which is polymerized to form thesecond portion. For example, the insert as described herein can beplaced on the first portion after the first portion has been partiallypolymerized such that the first portion is sufficiently viscous tosupport the insert. Additional precursor material can be placed in themold with the first portion supporting the insert as described herein,and cured to form second portion of the contact lens bonded to the firstportion of the contact lens away from the insert. The first portion andthe second portion can be formed from the same type of precursormaterial, for example. The insert can then be eroded as describedherein. The hydrated contact lens can be viewed with dark fieldmicroscopy as is known in the art, and the interface where the firstportion is bonded to the second portion detected. Although detectable bydark field microscopy in many instances, the interface does not produceartifacts that are perceptible to the user and the lens appearstransparent under normal bright field microscopy. The structure impartedon the inner surfaces of the contact lens body by the insert may also bedetected by dark field microscopy in at least some instances. Thecontact lens can be sectioned optically, or the contact lens can besectioned by mechanical cutting, and the interface may be observed withdark field microscopy.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

What is claimed is:
 1. A soft contact lens for correcting vision of aneye, comprising: a hydrogel contact lens body comprising water and across-linked polymer, wherein the contact lens body defines an internalcavity comprising a fluid and wherein the cross-linked polymer allowswater to diffuse in and out of the contact lens body to the cavity froman external surface of the contact lens body, and wherein the cavity isshaped to correct vision when in equilibrium with tear fluid of the eye.2. The soft contact lens of claim 1, wherein the contact lens body andthe cavity are configured together to increase optical power by at least2 D with an increase in internal pressure within a range from about 20Pascals (Pa) to about 50 Pa and wherein the cavity comprises a volumecontaining the first fluid within a range from about 0.5 mm³ to about 5mm³ and wherein the contact lens body comprises a modulus within a rangefrom about 0.25 MPa to about 2 MPa and wherein a hydrogel material ofthe contact lens body comprises an equilibrium water content within arange from about 30% to about 70%.
 3. The soft contact lens of claim 1,wherein the contact lens body comprises internal surfaces defining thecavity, the internal surfaces comprising internal surface structuresdefined with erosion of a material from within the cavity.
 4. The softcontact lens of claim 1, wherein the contact lens body comprises a firstportion on a first side of the cavity and a second portion of the secondside of the cavity with the cavity extending therebetween, the firstportion bonded to the second portion away from the cavity to containfluid within the cavity and optionally wherein an interface of the firstmaterial bonded to the second material is detectable by dark fieldmicroscopy.
 5. The soft contact lens of claim 1, wherein thecross-linked polymer directly contacts the fluid of the cavity.
 6. Thesoft contact lens of claim 1, wherein the cross-linked polymer comprisessufficient stiffness to retain a shape of an insert dissolved fromwithin the contact lens body to form the cavity.
 7. The soft contactlens of claim 1, wherein the cavity comprises a dissolved materialhaving a molecular weight within a range from about 3 to 7 k Daltons,and wherein the dissolved material is capable of diffusing through thecross-linked polymer of the contact lens body.
 8. The soft contact lensof claim 7, wherein the dissolved material comprises a material of aninsert dissolved to form the cavity.
 9. The soft contact lens of claim8, wherein the cavity comprises a shape profile corresponding to thedissolved insert.
 10. The soft contact lens of claim 1, wherein thecavity comprises an optical portion configured to correct vision of theeye and a lower portion fluidically coupled to the optical portion, andwherein the optical portion is configured to provide near visioncorrection when an eyelid engages the lower portion.
 11. The softcontact lens of claim 10, wherein the cross-linked polymer comprises asufficient amount of cross-linking to retain fluid in the opticalportion when the lower portion engages the eyelid to correct near visionof the eye.
 12. The soft contact lens of claim 10, wherein the contactlens body comprises one or more hinges coupled to the optical portionand the lower portion.
 13. The soft contact lens of claim 1, wherein thecavity comprises one or more internal structures shaped with an erodiblematerial.
 14. The soft contact lens of claim 1, wherein the cross-linkedpolymer comprises a hydrogel.
 15. The soft contact lens of claim 1,wherein the cavity is comprises a first fluid, not hermetically sealed,wherein the contact lens body is permeable to a second fluid in whichthe contact lens body is packaged, and the cavity is in equilibrium withthe second fluid in which the contact lens body is packaged.
 16. Thesoft contact lens of claim 1, wherein the cross-linked polymer comprisesa homogeneous polymer.
 17. The soft contact lens of claim 1, wherein thecross-linked polymer comprises a homopolymer.
 18. The soft contact lensof claim 1, wherein said polymer comprises hydrogel.
 19. The softcontact lens of claim 1, wherein the cross-linked polymer compriseschannels sized to permit diffusion of water between the cavity andoutside the contact lens body and to inhibit bacteria from entering thecavity from outside the contact lens body.
 20. The soft contact lens ofclaim 1, wherein the cross-linked polymer allows molecules having aradius of gyration of no more than 50 nm to diffuse through thecross-linked polymer of the contact lens body.
 21. The soft contact lensof claim 20, wherein the cross-linked polymer allows molecules having aradius of gyration of no more than 15 nm to diffuse through thecross-linked polymer of the contact lens body.
 22. The soft contact lensof claim 1, wherein the cavity comprises a dissolved material having amolecular weight within a range from about 3 to about 10 k Daltons, andwherein the dissolved material is capable of diffusing through thecross-linked polymer of the contact lens body.
 23. The soft contact lensof claim 1, wherein the cavity comprises a volume within a range fromabout 1 to 5 uL.
 24. The soft contact lens of claim 1, wherein the firstfluid comprises a refractive index within a range from about 1.31 toabout 1.37 and wherein the contact lens body comprises an index ofrefraction within a range from about 1.37 to about 1.48.
 25. The softcontact lens of claim 1, wherein the contact lens body has an anteriorside with an anterior thickness defined between an anterior surface ofthe contact lens body and an anterior surface of the internal cavity,and wherein the contact lens body has a posterior side with a posteriorthickness defined between a posterior surface of the contact lens bodyand a posterior surface of the inner cavity.
 26. The soft contact lensof claim 25, wherein the anterior thickness is less than the posteriorthickness.
 27. The soft contact lens of claim 25, wherein the anteriorthickness is within a range defined between any two of the followingvalues: about 10 microns, about 25 microns, about 50 microns, about 100microns, about 150 microns, and 200 microns.
 28. The soft contact lensof claim 25, wherein the posterior thickness is within a range definedbetween any two of the following values: about 10 microns, about 100microns, and about 200 microns.
 29. The soft contact lens of claim 25,wherein a thickness of the internal cavity from the anterior surface tothe posterior surface thereof is within a range defined between any twoof the following values: about 0.5 microns, about 15 microns, about 50microns, and about 100 microns.
 30. The soft contact lens of claim 25,wherein a thickness of the contact lens body from the anterior surfaceto the posterior surface thereof is in a range from about 80 microns toabout 250 microns.
 31. The soft contact lens of claim 1, wherein ashape-changing portion of the lens used to correct vision has RMSoptical path difference aberrations of about 0.4 microns or less in afar vision configuration when placed on an eye.
 32. The soft contactlens of claim 1, wherein an inner surface of the cross-linked polymerdefining the cavity comprises a shape profile corresponding to a solidmaterial dissolved to form the cavity.
 33. The soft contact lens ofclaim 32, wherein the inner surface of the cross-linked polymer definingthe cavity comprises a structure corresponding to the solid materialdissolved to form the cavity.
 34. The soft contact lens of claim 32,wherein the inner surface of the cavity comprises an optically smoothsurface over an inner portion of the cavity through which light passesto correct vision.
 35. The soft contact lens of claim 34, wherein theoptically smooth surface has a wavefront distortion of about 0.3 micronsor less measured through the optically smooth surface.
 36. The softcontact lens of claim 34, wherein the optically smooth surface comprisesno visually perceptible artifacts when worn by a patient.
 37. The softcontact lens of claim 34, wherein the optically smooth surface has anRMS value of about 0.2 microns or less.
 38. The soft contact lens ofclaim 32, wherein the inner surface of the cavity comprises a residualsurface structure from the solid material dissolved to form the cavity.39. The soft contact lens of claim 32, wherein the inner surface of thecavity has an RMS value of about 50 nm or less.
 40. The soft contactlens of claim 32, wherein the inner surface of the cavity has an RMSvalue in a range defined between any two of the following values: about5 nm, about 10 nm, about 15 nm, about 300 nm, about 500 nm, and about1000 nm.
 41. A soft contact lens for correcting vision of an eye,comprising: a hydrogel contact lens body comprising water and across-linked polymer, wherein the contact lens body defines an internalcavity comprising a fluid and wherein the cross-linked polymer allowswater to diffuse in and out of the contact lens body to the cavity froman external surface of the contact lens body, the contact lens bodycomprising an anterior surface and a posterior surface, the posteriorsurface and the anterior surface and the cavity shaped to correct visionwith the cavity in equilibrium with tear fluid of the eye.